Population-specific variations in KCNH2 predispose patients to delayed ventricular repolarization upon dihydroartemisinin-piperaquine therapy.

Dihydroartemisinin-piperaquine is efficacious for the treatment of uncomplicated malaria and its use is increasing globally. Despite the positive results in fighting malaria, inhibition of the Kv11.1 channel (hERG; encoded by the KCNH2 gene) by piperaquine has raised concerns about cardiac safety. Whether genetic factors could modulate the risk of piperaquine-mediated QT prolongations remained unclear. Here, we first profiled the genetic landscape of KCNH2 variability using data from 141,614 individuals. Overall, we found 1,007 exonic variants distributed over the entire gene body, 555 of which were missense. By optimizing the gene-specific parametrization of 16 partly orthogonal computational algorithms, we developed a KCNH2-specific ensemble classifier that identified a total of 116 putatively deleterious missense variations. To evaluate the clinical relevance of KCNH2 variability, we then sequenced 293 Malian patients with uncomplicated malaria and identified 13 variations within the voltage sensing and pore domains of Kv11.1 that directly interact with channel blockers. Cross-referencing of genetic and electrocardiographic data before and after piperaquine exposure revealed that carriers of two common variants, rs1805121 and rs41314375, experienced significantly higher QT prolongations (ΔQTc of 41.8 ms and 61 ms, respectively, vs 14.4 ms in controls) with more than 50% of carriers having increases in QTc >30 ms. Furthermore, we identified three carriers of rare population-specific variations who experienced clinically relevant delayed ventricular repolarization. Combined, our results map population-scale genetic variability of KCNH2 and identify genetic biomarkers for piperaquine-induced QT prolongation that could help to flag at-risk patients and optimize efficacy and adherence to antimalarial therapy.

Improving testing capacity for COVID-19: experiences and lessons from Senegal, Uganda, Nigeria, and the Democratic Republic of Congo.

Background: African countries leveraged testing capacities to enhance public health action in response to the COVID-19 pandemic. This paper describes experiences and lessons learned during the improvement of testing capacity throughout the COVID-19 response in Senegal, Uganda, Nigeria, and the Democratic Republic of the Congo (DRC). Methods: The four countries' testing strategies were studied using a mixed-methods approach. Desk research on COVID-19 testing strategies was conducted and complemented by interviewing key informants. The findings were synthesized to demonstrate learning outcomes across the four countries. Results: The four countries demonstrated severely limited testing capacities at the onset of the pandemic. These countries decentralized COVID-19 testing services by leveraging preexisting laboratory systems such as PCR and GeneXpert used for the diagnosis of tuberculosis (TB) to address this gap and the related inequities, engaging the private sector, establishing new laboratories, and using rapid diagnostic tests (RDTs) to expand testing capacity and reduce the turnaround time (TAT). The use of digital platforms improved the TAT. Testing supplies were sourced through partners, although access to global markets was challenging. Case detection remains suboptimal due to high costs, restrictive testing strategies, testing access challenges, and misinformation, which hinder the demand for testing. The TAT for PCR remained a challenge, while RDT use was underreported, although Senegal manufactured RDTs locally. Key findings indicate that regionally coordinated procurement and manufacturing mechanisms are required, that testing modalities must be simplified for improved access, and that the risk-based testing strategy limits comprehensive understanding of the disease burden. Conclusion: Although testing capacities improved significantly during the pandemic, case detection and access to testing remained suboptimal. The four countries could benefit from further simplification of testing modalities and cost reduction. Local manufacturing and pooled procurement mechanisms for diagnostics are needed for optimal pandemic preparedness and response.

The Prevalence of Human Plasmodium Species during Peak Transmission Seasons from 2016 to 2021 in the Rural Commune of Ntjiba, Mali.

Up-to-date knowledge of key epidemiological aspects of each Plasmodium species is necessary for making informed decisions on targeted interventions and control strategies to eliminate each of them. This study aims to describe the epidemiology of plasmodial species in Mali, where malaria is hyperendemic and seasonal. Data reports collected during high-transmission season over six consecutive years were analyzed to summarize malaria epidemiology. Malaria species and density were from blood smear microscopy. Data from 6870 symptomatic and 1740 asymptomatic participants were analyzed. The median age of participants was 12 years, and the sex ratio (male/female) was 0.81. Malaria prevalence from all Plasmodium species was 65.20% (95% CI: 60.10-69.89%) and 22.41% (CI: 16.60-28.79%) for passive and active screening, respectively. P. falciparum was the most prevalent species encountered in active and passive screening (59.33%, 19.31%). This prevalence was followed by P. malariae (1.50%, 1.15%) and P. ovale (0.32%, 0.06%). Regarding frequency, P. falciparum was more frequent in symptomatic individuals (96.77% vs. 93.24%, p = 0.014). In contrast, P. malariae was more frequent in asymptomatic individuals (5.64% vs. 2.45%, p < 0.001). P. ovale remained the least frequent species (less than 1%), and no P. vivax was detected. The most frequent coinfections were P. falciparum and P. malariae (0.56%). Children aged 5-9 presented the highest frequency of P. falciparum infections (41.91%). Non-falciparum species were primarily detected in adolescents (10-14 years) with frequencies above 50%. Only P. falciparum infections had parasitemias greater than 100,000 parasites per µL of blood. P. falciparum gametocytes were found with variable prevalence across age groups. Our data highlight that P. falciparum represented the first burden, but other non-falciparum species were also important. Increasing attention to P. malariae and P. ovale is essential if malaria elimination is to be achieved.

Spread and seasonality of COVID-19 pandemic confirmed cases in sub-Saharan Africa: experience from Democratic Republic of Congo, Nigeria, Senegal, and Uganda.

BACKGROUND: The COVID-19 pandemic has impacted the world negatively with huge health and socioeconomic consequences. This study estimated the seasonality, trajectory, and projection of COVID-19 cases to understand the dynamics of the disease spread and inform response interventions. METHOD: Descriptive analysis of daily confirmed COVID-19 cases from January 2020 to 12th March 2022 was conducted in four purposefully selected sub-Saharan African countries (Nigeria, Democratic Republic of Congo (DRC), Senegal, and Uganda). We extrapolated the COVID-19 data from (2020 to 2022) to 2023 using a trigonometric time series model. A decomposition time series method was used to examine the seasonality in the data. RESULTS: Nigeria had the highest rate of spread (ß) of COVID-19 (ß = 381.2) while DRC had the least rate (ß = 119.4). DRC, Uganda, and Senegal had a similar pattern of COVID-19 spread from the onset through December 2020. The average doubling time in COVID-19 case count was highest in Uganda (148 days) and least in Nigeria (83 days). A seasonal variation was found in the COVID-19 data for all four countries but the timing of the cases showed some variations across countries. More cases are expected in the 1st (January-March) and 3rd (July-September) quarters of the year in Nigeria and Senegal, and in the 2nd (April-June) and 3rd (October-December) quarters in DRC and Uganda. CONCLUSION: Our findings show a seasonality that may warrant consideration for COVID-19 periodic interventions in the peak seasons in the preparedness and response strategies.

Endoscopie digestive haute à l'hôpital national de Zinder: indications et résultats / Upper digestive endoscopy at Zinder National Hospital: indications and results

Objectif : déterminer les indications et résultats de l'endoscopie digestive haute (EDH) à l'Hôpital National de Zinder. Matériels et méthodes : il s'agit d'une analyse rétrospective des comptes rendus d'EDH, à partir des registres d'endoscopie digestive du 1er Janvier 2020 au 28 Février 2021, portant sur 667 examens, soit une fréquence mensuelle de 48 EDH. . Résultats : l'âge moyen des patients était de 38,98±14,84 (13-80 ans) avec un sex ratio de 1,02. Les épigastralgies représentent 42,8% (n= 363) d'indication d'EDH, la dyspepsie 15,2% (n=129), les douleurs abdominales diffuses 11,9% (n= 101), les vomissements 8,1% (n= 69), la recherche des signes endoscopiques d'hypertension portale 5,1% (n= 43), la dysphagie 4,9% (n=42) et les hémorragies digestives 3,2% (n=27). Selon le segment anatomique concerné, l'estomac comptait pour 55,51% (n=419), l'œsophage 19,6% (n=148) et le duodénum 6,68% (n=50). Les lésions inflammatoires représentent 63,04% (n=475), les ulcères 6,65% (n=50), les tumeurs 3,03% (n=23) et les lésions diverses 27,28% (n=205). La biopsie était réalisée chez 22 patients (3,46%) et 10 comptes rendus histologiques étaient parvenus, repartis en 06 adénocarcinomes gastriques, 02 gastriques chroniques avec métaplasie intestinale, 01 carcinome épidermoÏde de l'œsophage et 01 polype gastrique hyperplasique. Conclusion : Les épigastralgies dominent les indications de l'EDH. La pathologie digestive haute est certes dominée par les lésons inflammatoires, mais les ulcères et les tumeurs sont de plus en plus diagnostiqués. Ces lésions allaient être mieux évaluées si des biopsies systématiques étaient réalisées chez nos patient

Objective: to determine the indications and results of upper digestive endoscopy (EDH) at the Zinder National Hospital. Materials and methods: this is a retrospective analysis of EDH reports, from digestive endoscopy registers from January 1, 2020 to February 28, 2021, covering 667 examinations, or a monthly frequency of 48 EDH. Results: the average age of patients was 38.98±14.84 (13-80 years) with a sex ratio of 1.02. Epigastralgia represents 42.8% (n = 363) of indication of EDH, dyspepsia 15.2% (n = 129), diffuse abdominal pain 11.9% (n = 101), vomiting 8.1% (n = 69), search for endoscopic signs of portal hypertension 5.1% (n = 43), dysphagia 4.9% (n = 42) and digestive hemorrhages 3.2% (n = 27Depending on the anatomical segment concerned, the stomach accounted for 55.51% (n=419), the esophagus 19.6% (n=148) and the duodenum 6.68% (n=50). Inflammatory lesions account for 63.04% (n=475), ulcers 6.65% (n=50), tumours 3.03% (n=23) and miscellaneous lesions 27.28% (n=205). The biopsy was performed in 22 patients (3.46%) and 10 histological reports were obtained, divided into 06 gastric adenocarcinomas, 02 chronic gastric with intestinal metaplasia, 01 epidermoidal carcinoma of the esophagus and 01 hyperplastic gastric polypConclusion: Epigastralgia dominates the indications of HRE. Upper digestive pathology is certainly dominated by inflammatory lesons, but ulcers and tumors are increasingly diagnosed. These lesions would be better evaluated if systematic biopsies were performed in our patients

A Novel Ex Vivo Drug Assay for Assessing the Transmission-Blocking Activity of Compounds on Field-Isolated Plasmodium falciparum Gametocytes.

The discovery and development of transmission-blocking therapies challenge malaria elimination and necessitate standard and reproducible bioassays to measure the blocking properties of antimalarial drugs and candidate compounds. Most of the current bioassays evaluating the transmission-blocking activity of compounds rely on laboratory-adapted Plasmodium strains. Transmission-blocking data from clinical gametocyte isolates could help select novel transmission-blocking candidates for further development. Using freshly collected Plasmodium falciparum gametocytes from asymptomatic individuals, we first optimized ex vivo culture conditions to improve gametocyte viability and infectiousness by testing several culture parameters. We next pre-exposed ex vivo field-isolated gametocytes to chloroquine, dihydroartemisinin, primaquine, KDU691, GNF179, and oryzalin for 48 h prior to direct membrane feeding. We measured the activity of the drug on the ability of gametocytes to resume the sexual life cycle in Anopheles after drug exposure. Using 57 blood samples collected from Malian volunteers aged 6 to 15 years, we demonstrate that the infectivity of freshly collected field gametocytes can be preserved and improved ex vivo in a culture medium supplemented with 10% horse serum at 4% hematocrit for 48 h. Moreover, our optimized drug assay displays the weak transmission-blocking activity of chloroquine and dihydroartemisinin, while primaquine and oryzalin exhibited a transmission-blocking activity of ~50% at 1 µM. KDU691 and GNF179 both interrupted Plasmodium transmission at 1 µM and 5 nM, respectively. This new approach, if implemented, has the potential to accelerate the screening of compounds with transmission-blocking activity.

Private sector engagement in the COVID-19 response: experiences and lessons from the Democratic Republic of Congo, Nigeria, Senegal and Uganda.

BACKGROUND: Private entities play a major role in health globally. However, their contribution has not been fully optimized to strengthen delivery of public health services. The COVID-19 pandemic has overwhelmed health systems and precipitated coalitions between public and private sectors to address critical gaps in the response. We conducted a study to document the public and private sector partnerships and engagements to inform current and future responses to public health emergencies. METHODS: This was a multi-country cross-sectional study conducted in the Democratic Republic of Congo, Nigeria, Senegal and Uganda between November 2020 and March 2021 to assess responses to the COVID-19 pandemic. We conducted a scoping literature review and key informant interviews (KIIs) with private and public health sector stakeholders. The literature reviewed included COVID-19 country guidelines and response plans, program reports and peer-reviewed and non-peer-reviewed publications. KIIs elicited information on country approaches and response strategies specifically the engagement of the private sector in any of the strategic response operations. RESULTS: Across the 4 countries, private sector strengthened laboratory systems, COVID-19 case management, risk communication and health service continuity. In the DRC and Nigeria, private entities supported contact tracing and surveillance activities. Across the 4 countries, the private sector supported expansion of access to COVID-19 testing services through establishing partnerships with the public health sector albeit at unregulated fees. In Senegal and Uganda, governments established partnerships with private sector to manufacture COVID-19 rapid diagnostic tests. The private sector also contributed to treatment and management of COVID-19 cases. In addition, private entities provided personal protective equipment, conducted risk communication to promote adherence to safety procedures and health promotion for health service continuity. However, there were concerns related to reporting, quality and cost of services, calling for quality and price regulation in the provision of services. CONCLUSIONS: The private sector contributed to the COVID-19 response through engagement in COVID-19 surveillance and testing, management of COVID-19 cases, and health promotion to maintain health access. There is a need to develop regulatory frameworks for sustainable public-private engagements including regulation of pricing, quality assurance and alignment with national plans and priorities during response to epidemics.

Polymicrogyria, aventriculy, polydactyly, encephalocele, callosal agenesis (PAPEC): a new syndrome?

INTRODUCTION: Aventriculy is a very rare observation and is generally associated with holoprosencephaly. We report here a case of polymalformation affecting the brain, hands, and feet observed in a highly consanguineous family in Niger. CASE REPORT: A boy was born from a highly consanguineous family presenting multiple malformations (aventriculy, extreme microcephaly, polydactyly, polymicrogyria, callosal agenesis, and parietal encephalocele). To the best of our knowledge, such association has never been reported so far. DISCUSSION: We propose to name this association PAPEC (for polymicrogyria, aventriculy, polydactyly, encephalocele, and callosal agenesis). The occurrence of this disease in a highly consanguineous family suggests a genetic origin. Furthermore, we propose hypotheses that could explain pathophysiology of this defect.

Assessment of Comamonas testosteroni strain PT9 as a rapid phthalic acid degrader for industrial wastewaters.

In this study, characterization of industry-borne Comamonas testosteroni strain PT9 isolate was performed by determining degradation ability on phthalic acid (PA). High-performance liquid chromatography analyses showed that strain PT9 completely degraded 102.94 mg/L of PA within 6 h. Viability polymerase chain reaction (vPCR) was performed with propidium monoazide treatment. vPCR showed that the PA has positively stimulated the cell growth during degradation. To consider the fate of PA, the proposed catalytic genes (ophA2, iphA2, tphA2, tphA3, pmdA, and pmdB) for the degradation pathways of PA isomers for C. testosteroni were screened in strain PT9. All genes except iphA2 were detected in strain PT9, and expression levels of related genes were analyzed by Real-Time PCR (qPCR).

[Upper Digestive Endoscopy at Zinder National Hospital: Indications and Results]. / Endoscopie Digestive Haute a L'hopital National de Zinder: Indications et Resultats.

OBJECTIVE: to determine the indications and results of upper digestive endoscopy (EDH) at the Zinder National Hospital. MATERIALS AND METHODS: this is a retrospective analysis of EDH reports, from digestive endoscopy registers from January 1, 2020 to February 28, 2021, covering 667 examinations, or a monthly frequency of 48 EDH. RESULTS: the average age of patients was 38.98±14.84 (13-80 years) with a sex ratio of 1.02. Epigastralgia represents 42.8% (n = 363) of indication of EDH, dyspepsia 15.2% (n = 129), diffuse abdominal pain 11.9% (n = 101), vomiting 8.1% (n = 69), search for endoscopic signs of portal hypertension 5.1% (n = 43), dysphagia 4.9% (n = 42) and digestive hemorrhages 3.2% (n = 27Depending on the anatomical segment concerned, the stomach accounted for 55.51% (n=419), the esophagus 19.6% (n=148) and the duodenum 6.68% (n=50). Inflammatory lesions account for 63.04% (n=475), ulcers 6.65% (n=50), tumours 3.03% (n=23) and miscellaneous lesions 27.28% (n=205). The biopsy was performed in 22 patients (3.46%) and 10 histological reports were obtained, divided into 06 gastric adenocarcinomas, 02 chronic gastric with intestinal metaplasia, 01 epidermoidal carcinoma of the esophagus and 01 hyperplastic gastric polyp. CONCLUSION: Epigastralgia dominates the indications of HRE. Upper digestive pathology is certainly dominated by inflammatory lesons, but ulcers and tumors are increasingly diagnosed. These lesions would be better evaluated if systematic biopsies were performed in our patients.

OBJECTIF: déterminer les indications et résultats de l'endoscopie digestive haute (EDH) à l'Hôpital National de Zinder. MATÉRIELS ET MÉTHODES: il s'agit d'une analyse rétrospective des comptes rendus d'EDH, à partir des registres d'endoscopie digestive du 1er Janvier 2020 au 28 Février 2021, portant sur 667 examens, soit une fréquence mensuelle de 48 EDH. . RÉSULTATS: l'âge moyen des patients était de 38,98±14,84 (13-80 ans) avec un sex ratio de 1,02. Les épigastralgies représentent 42,8% (n=363) d'indication d'EDH, la dyspepsie 15,2% (n=129), les douleurs abdominales diffuses 11,9% (n=101), les vomissements 8,1% (n= 69), la recherche des signes endoscopiques d'hypertension portale 5,1% (n= 43), la dysphagie 4,9% (n=42) et les hémorragies digestives 3,2% (n=27). Selon le segment anatomique concerné, l'estomac comptait pour 55,51% (n=419), l'œsophage 19,6% (n=148) et le duodénum 6,68% (n=50). Les lésions inflammatoires représentent 63,04% (n=475), les ulcères 6,65% (n=50), les tumeurs 3,03% (n=23) et les lésions diverses 27,28% (n=205). La biopsie était réalisée chez 22 patients (3,46%) et 10 comptes rendus histologiques étaient parvenus, repartis en 06 adénocarcinomes gastriques, 02 gastriques chroniques avec métaplasie intestinale, 01 carcinome épidermoïde de l'œsophage et 01 polype gastrique hyperplasique. CONCLUSION: Les épigastralgies dominent les indications de l'EDH. La pathologie digestive haute est certes dominée par les lésons inflammatoires, mais les ulcères et les tumeurs sont de plus en plus diagnostiqués. Ces lésions allaient être mieux évaluées si des biopsies systématiques étaient réalisées chez nos patients.

Characteristics and correlates of U.S. clinicians prescribing buprenorphine for opioid use disorder treatment using expanded authorities during the COVID-19 pandemic.

BACKGROUND: To determine how clinicians with a DATA waiver to prescribe buprenorphine for opioid use disorder (OUD) adapted during the COVID-19 pandemic to emergency authorities, including use of telehealth to prescribe buprenorphine, the challenges faced by clinicians, and strategies employed by them to manage patients with OUD. METHODS: From June 23, 2020 to August 19, 2020, we conducted an electronic survey of U.S. DATA-waivered clinicians. Descriptive statistics and multivariable logistic regression were used for analysis. RESULTS: Among 10,238 respondents, 68 % were physicians, 25 % nursing-related providers, and 6% physician assistants; 28 % reported never prescribing or not prescribing in the 12 months prior to the survey. Among the 72 % of clinicians who reported past 12-month buprenorphine prescribing (i.e. active practitioners during the pandemic) 30 % reported their practice setting closed to in-person visits during COVID-19; 33 % reported remote prescribing to new patients without an in-person examination. The strongest predictors of remote buprenorphine prescribing to new patients were prescribing buprenorphine to larger numbers of patients in an average month in the past year and closure of the practice setting during the pandemic; previous experience with remote prescribing to established patients prior to COVID-19 also was a significant predictor. Among clinicians prescribing to new patients without an in-person examination, 5.5 % reported difficulties with buprenorphine induction, most commonly withdrawal symptoms. CONCLUSIONS: Telehealth practices and prescribing to new patients without an in-person examination were adopted by DATA-waivered clinicians during the first six months of COVID-19. Permanent adoption of these authorities may enable expanded access to buprenorphine treatment.

Uptake of Plasmodium falciparum Gametocytes During Mosquito Bloodmeal by Direct and Membrane Feeding.

Plasmodium falciparum remains one of the leading causes of child mortality, and nearly half of the world's population is at risk of contracting malaria. While pathogenesis results from replication of asexual forms in human red blood cells, it is the sexually differentiated forms, gametocytes, which are responsible for the spread of the disease. For transmission to succeed, both mature male and female gametocytes must be taken up by a female Anopheles mosquito during its blood meal for subsequent differentiation into gametes and mating inside the mosquito gut. Observed circulating numbers of gametocytes in the human host are often surprisingly low. A pre-fertilization behavior, such as skin sequestration, has been hypothesized to explain the efficiency of human-to-mosquito transmission but has not been sufficiently tested due to a lack of appropriate tools. In this study, we describe the optimization of a qPCR tool that enables the relative quantification of gametocytes within very small input samples. Such a tool allows for the quantification of gametocytes in different compartments of the host and the vector that could potentially unravel mechanisms that enable highly efficient malaria transmission. We demonstrate the use of our gametocyte quantification method in mosquito blood meals from both direct skin feeding on Plasmodium gametocyte carriers and standard membrane feeding assay. Relative gametocyte abundance was not different between mosquitoes fed through a membrane or directly on the skin suggesting that there is no systematic enrichment of gametocytes picked up in the skin.

Population Pharmacokinetic Properties of Sulfadoxine and Pyrimethamine: a Pooled Analysis To Inform Optimal Dosing in African Children with Uncomplicated Malaria.

Sulfadoxine-pyrimethamine with amodiaquine is recommended by the World Health Organization as seasonal malaria chemoprevention for children aged 3 to 59 months in the sub-Sahel regions of Africa. Suboptimal dosing in children may lead to treatment failure and increased resistance. Pooled individual patient data from four previously published trials on the pharmacokinetics of sulfadoxine and pyrimethamine in 415 pediatric and 386 adult patients were analyzed using nonlinear mixed-effects modeling to evaluate the current dosing regimen and, if needed, to propose an optimized dosing regimen for children under 5 years of age. The population pharmacokinetics of sulfadoxine and pyrimethamine were both best described by a one-compartment disposition model with first-order absorption and elimination. Body weight, age, and nutritional status (measured as the weight-for-age Z-score) were found to be significant covariates. Allometric scaling with total body weight and the maturation of clearance in children by postgestational age improved the model fit. Underweight-for-age children were found to have 15.3% and 26.7% lower bioavailabilities of sulfadoxine and pyrimethamine, respectively, for each Z-score unit below -2. Under current dosing recommendations, simulation predicted that the median day 7 concentration was below the 25th percentile for a typical adult patient (50 kg) for sulfadoxine for patients in the weight bands of 8 to 9, 19 to 24, 46 to 49, and 74 to 79 kg and for pyrimethamine for patients in the weight bands of 8 to 9, 14 to 24, and 42 to 49 kg. An evidence-based dosing regimen was constructed that would achieve sulfadoxine and pyrimethamine exposures in young children and underweight-for-age young children that were similar to those currently seen in a typical adult.

Long-term results of fractionated stereotactic radiotherapy as third-line treatment in acromegaly.

The treatment of acromegaly is based on surgery, drugs, and radiotherapy as a third-line option. Fractionated stereotactic radiotherapy (FSRT) is a new technique with a need for long-term evaluation. The purpose of the study was to evaluate long-term results of FSRT in acromegaly. Overall, 34 patients [sex ratio 1.12, age 45 (5-65) years] with a pituitary adenoma of 24.5 (9-76) mm including 20 invasive tumors were treated by radiotherapy in fractionated stereotactic conditions delivering 50 gy in 27 sessions. Baseline growth hormone (GH) and IGF1 levels were 18 (±14.5) and 632.6 (±339) µg/L, respectively. Indications of FSRT were failure of surgery and drug treatments (n = 30) or contraindication/refusal of surgery (n = 4). Hormonal control was defined by normal age- and sex-adjusted IGF1. Remission was defined by hormonal control after withdrawal of drugs for a minimum of three consecutive months. Data were analyzed in SPSS software with a significance level at p < 0.05. After a mean follow-up of 152 months, hormonal control was achieved in 33 patients (97 %) with withdrawal of drugs in 13 patients (38.2 %) without any recurrence. Factors found to be significantly associated to remission in a multivariate Cox regression were lower baseline hormone levels (GH and IGF1) and smaller tumor size. Tumor control was achieved in all patients. Acquired hypopituitarism after radiotherapy was the main side effect reported with a rate of 39 %. FSRT seems to be an effective and well tolerated third-line treatment of acromegaly, particularly adapted to macro adenomas treatment.

Implementation of a high-dose-rate brachytherapy program for carcinoma of the cervix in Senegal: a pragmatic model for the developing world.

West Africa has one of the highest incidence rates of carcinoma of the cervix in the world. The vast majority of women do not have access to screening or disease treatment, leading to presentation at advanced stages and to high mortality rates. Compounding this problem is the lack of radiation treatment facilities in Senegal and many other parts of the African continent. Senegal, a country of 13 million people, had a single (60)Co teletherapy unit before our involvement and no brachytherapy capabilities. Radiating Hope, a nonprofit organization whose mission is to provide radiation therapy equipment to countries in the developing world, provided a high-dose-rate afterloading unit to the cancer center for curative cervical cancer treatment. Here we describe the implementation of high-dose-rate brachytherapy in Senegal requiring a nonstandard fractionation schedule and a novel treatment planning approach as a possible blueprint to providing this technology to other developing countries.

Adenomyosis in the bovine uterus: correlation between frequency, age, and 17ß-estradiol-progesterone equilibrium.

Adenomyosis of the uterus is characterized by the presence of islands of endometrial glands and stroma within the myometrium. Etiopathology of adenomyosis has not been clearly defined but it potentially interferes reproductive processes in cattle. The aim of this initial study was to evaluate the impact of age on the frequency of adenomyosis in cows. Endometrial tissues collected from cows slaughtered between Day 8 and 12 of the estrous cycle (N = 72) were divided into two age groups: (1) 2 to 4 years old (N = 36) and (2) 5 years old and older (N = 36). The tissues were stained with hematoxylin and eosin. The adenomyosis histopathomorphologic stage was classified on a four-point scale according to the penetration of endometrial structures inside the perimetrium. The protein expression of the 17-ß estradiol (E2) and progesterone (P4) receptors were evaluated in the endometrial tissue samples by immunohistochemistry and Western blot analysis, and E2 and P4 concentrations were measured in the peripheral blood and uterine tissue. Adenomyosis was observed in 38 of the cows examined including 13 of the 2- to 4-year-old cows and 25 of the cows 5 years old or older. The frequency and intensity of adenomyosis increased with age. Higher E2 receptor protein expression was observed in adenomyotic cows and increased with disease development and increase of number of glands inside the uterus in the direction of perimetrium, and P4 receptor protein expression were unchanged in healthy and adenomyotic cows. An increase in the expression of E2 receptors and high, supraphysiological levels of E2 was detected in cows with III and IV degree of adenomyosis (P < 0.05). Overexpression of E2 receptor and alternations in E2 secretion might make the bovine uterus susceptible to a growth advantage of adenomyotic tissue over the surrounding myometrium. The pathogenesis and immunoendocrine mechanisms controlling adenomyosis in cattle warrant further study.

Quinine treatment selects the pfnhe-1 ms4760-1 polymorphism in Malian patients with Falciparum malaria.

BACKGROUND: The mechanism of Plasmodium falciparum resistance to quinine is not known. In vitro quantitative trait loci mapping suggests involvement of a predicted P. falciparum sodium-hydrogen exchanger (pfnhe-1) on chromosome 13. METHODS: We conducted prospective quinine efficacy studies in 2 villages, Kollé and Faladié, Mali. Cases of clinical malaria requiring intravenous therapy were treated with standard doses of quinine and followed for 28 days. Treatment outcomes were classified using modified World Health Organization protocols. Molecular markers of parasite polymorphisms were used to distinguish recrudescent parasites from new infections. The prevalence of pfnhe-1 ms4760-1 among parasites before versus after quinine treatment was determined by direct sequencing. RESULTS: Overall, 163 patients were enrolled and successfully followed. Without molecular correction, the mean adequate clinical and parasitological response (ACPR) was 50.3% (n = 163). After polymerase chain reaction correction to account for new infections, the corrected ACPR was 100%. The prevalence of ms4760-1 increased significantly, from 26.2% (n = 107) before quinine treatment to 46.3% (n = 54) after therapy (P = .01). In a control sulfadoxine-pyrimethamine study, the prevalence of ms4760-1 was similar before and after treatment. CONCLUSIONS: This study supports a role for pfnhe-1 in decreased susceptibility of P. falciparum to quinine in the field.

Scale-up of home-based management of malaria based on rapid diagnostic tests and artemisinin-based combination therapy in a resource-poor country: results in Senegal.

BACKGROUND: Effective case management of malaria requires prompt diagnosis and treatment within 24 hours. Home-based management of malaria (HMM) improves access to treatment for populations with limited access to health facilities. In Senegal, an HMM pilot study in 2008 demonstrated the feasibility of integrated use of RDTs and ACT in remote villages by volunteer Home Care Providers (HCP). Scale-up of the strategy began in 2009, reaching 408 villages in 2009 and 861 villages in 2010. This paper reports the results of the scale-up in the targeted communities and the impact of the strategy on malaria in the formal health sector. METHODS: Data reported by the HCPs were used to assess their performance in 2009 and 2010, while routine malaria morbidity and mortality data were used to assess the impact of the HMM programme. Two high transmission regions where HMM was not implemented until 2010 were used as a comparison. RESULTS AND DISCUSSION: From July 2009 through May 2010, 12582 suspected cases were managed by HCPs, 93% (11672) of whom were tested with an RDT. Among those tested, 37% (4270) had a positive RDT, 97% (4126) of whom were reported treated and cured. Home care providers referred 6871 patients to health posts for management: 6486 with a negative RDT, 119 infants < 2 months, 105 pregnant women, and 161 severe cases. There were no deaths among these patients. In 2009 compared to 2008, incidence of suspected and confirmed malaria cases, all hospitalizations and malaria-related hospitalizations decreased in both intervention and comparison regions. Incidence of in-hospital deaths due to malaria decreased by 62.5% (95% CI 43.8-81.2) in the intervention regions, while the decrease in comparison regions was smaller and not statistically significant. CONCLUSION: Home-based management of malaria including diagnosis with RDT and treatment based on test results is a promising strategy to improve the access of remote populations to prompt and effective management of uncomplicated malaria and to decrease mortality due to malaria. When scaled-up to serve remote village communities in the regions of Senegal with the highest malaria prevalence, home care providers demonstrated excellent adherence to guidelines, potentially contributing to a decrease in hospital deaths attributed to malaria.

A cross-sectional evaluation of venous thromboembolism risk and use of venous thromboembolism prophylaxis in hospitalized patients in Senegal.

BACKGROUND: Venous thromboembolism is a common and preventable cause of morbidity and mortality in hospitalized patients. There is a lack of data on the distribution of risk factors and prophylaxis practices in sub-Saharan Africa. AIM: To assess the prevalence of venous thromboembolism risk in hospitalized patients and to determine the proportion of at-risk patients who receive prophylaxis. METHODS: The study was a cross-sectional hospital-based survey. On the basis of the global ENDORSE methodology, patients aged≥40 years admitted to a medical ward or those aged≥18 years admitted to a surgical ward were assessed for risk of venous thromboembolism by hospital chart review. Distribution of risk factors and coverage of prophylaxis in at-risk patients were determined using the 2004 American College of Chest Physicians evidence-based consensus guidelines. RESULTS: From October to November 2008, 520 patients (278 medical; 242 surgical) were enrolled in 12 hospitals across Senegal. Two hundred and ninety-eight (57%) were at risk of venous thromboembolism; 152 (57.4%) medical patients and 146 (60.3%) surgical patients. Among those at risk, 48 (31.6%) medical patients and 52 (35.6%) surgical patients received a prescription for prophylaxis. Among patients without contraindication to anticoagulants, 33.8% (46/136) on medical wards and 37.5% (48/128) on surgical wards received prophylaxis. CONCLUSION: The risk of venous thromboembolism was frequent in hospitalized patients in Senegal but only a few received the recommended prophylaxis. There is a need to implement a programme to improve venous thromboembolism awareness and prophylaxis.

Effects of amodiaquine and artesunate on sulphadoxine-pyrimethamine pharmacokinetic parameters in children under five in Mali.

BACKGROUND: Sulphadoxine-pyrimethamine, in combination with artesunate or amodiaquine, is recommended for the treatment of uncomplicated malaria and is being evaluated for intermittent preventive treatment. Yet, limited data is available on pharmacokinetic interactions between these drugs. METHODS: In a randomized controlled trial, children aged 6-59 months with uncomplicated falciparum malaria, received either one dose of sulphadoxine-pyrimethamine alone (SP), one dose of SP plus three daily doses of amodiaquine (SP+AQ) or one dose of SP plus 3 daily doses of artesunate (SP+AS). Exactly 100 µl of capillary blood was collected onto filter paper before drug administration at day 0 and at days 1, 3, 7, 14, 21 and 28 after drug administration for analysis of sulphadoxine and pyrimethamine pharmacokinetic parameters. RESULTS: Fourty, 38 and 31 patients in the SP, SP+AQ and SP+AS arms, respectively were included in this study. The concentrations on day 7 (that are associated with therapeutic efficacy) were similar between the SP, SP+AQ and SP+AS treatment arms for sulphadoxine (median [IQR] 35.25 [27.38-41.70], 34.95 [28.60-40.85] and 33.40 [24.63-44.05] µg/mL) and for pyrimethamine (56.75 [46.40-92.95], 58.75 [43.60-98.60] and 59.60 [42.45-86.63] ng/mL). There were statistically significant differences between the pyrimethamine volumes of distribution (4.65 [3.93-6.40], 4.00 [3.03-5.43] and 5.60 [4.40-7.20] L/kg; p = 0.001) and thus elimination half-life (3.26 [2.74 -3.82], 2.78 [2.24-3.65] and 4.02 [3.05-4.85] days; p < 0.001). This study confirmed the lower SP concentrations previously reported for young children when compared with adult malaria patients. CONCLUSION: Despite slight differences in pyrimethamine volumes of distribution and elimination half-life, these data show similar exposure to SP over the critical initial seven days of treatment and support the current use of SP in combination with either AQ or AS for uncomplicated falciparum malaria treatment in young Malian children.