Cholera‐schistosomiasis coinfection dynamics

The present work investigates the coinfection dynamics of the cholera and schistosomiasis diseases. The steady states of the model are examined. We obtain results for the model in detail and present the stability results whenever the basic reproduction number is less than unity ( ). For each submodel, the existence of backward bifurcation is presented and for the coinfection model. Furthermore, we formulate an optimal control problem with an appropriate set of control variables. The optimal control problem and the associated results are derived and discussed. The optimal control problem and the suggested controls are utilized to obtain optimal control characterizations. Numerical results are presented by choosing various optimal control strategies for the early elimination of both infections from the population. It is suggested that appropriate uses and application to the population could significantly reduce the infection. Therefore, based on our findings, we suggest to the public health department that the only possible cost‐effective strategy for the elimination of schistosomiasis and cholera coinfection is the combination of both diseases' preventive measures and the treatment of schistosomiasis.     

Confronting TB/HIV in the era of increasing anti‐TB drug resistance

HIV associated TB is a major public health problem. In 2006, it was estimated that there were over 700,000 people who suffered from HIV associated TB, of whom about 200, 000 have died. The burden of HIV associated TB is greatest in Sub‐Saharan Africa where the TB epidemic is primarily driven by HIV. There has been steady progress made in reducing the burden of HIV in TB patients with an increasing number of TB patients tested for HIV and provided with cotrimoxazole preventive therapy (CPT) and anti‐retroviral treatment (ART). Less progress is being made to reduce the burden of TB in people living with HIV. The number of HIV infected persons reported to have been screened for TB was less than 1% while Isoniazid preventive therapy was reported to have been provided to less than 0.1% of eligible persons in 2006. A major push is urgently needed to accelerate the implementation of three important interventions. The three are Intensified TB Screening (ICF) among people living with HIV, the provision of Isoniazid Preventive Therapy (IPT) and TB Infection Control(IC). These interventions are best carried out by HIV control programmes which should therefore be encouraged to take greater responsibility in implementing these interventions.     

On the optimal control for fractional multi‐strain TB model

In this paper, optimal control of a general nonlinear multi‐strain tuberculosis (TB) model that incorporates three strains drug‐sensitive, emerging multi‐drug resistant and extensively drug‐resistant is presented. The general multi‐strain TB model is introduced as a fractional order multi‐strain TB model. The fractional derivatives are described in the Caputo sense. An optimal control problem is formulated and studied theoretically using the Pontryagin maximum principle. Four controls variables are proposed to minimize the cost of interventions. Two simple‐numerical methods are used to study the nonlinear fractional optimal control problem. The methods are the iterative optimal control method and the generalized Euler method. Comparative studies are implemented, and it is found that the iterative optimal control method is better than the generalized Euler method. Copyright © 2016 John Wiley & Sons, Ltd.     

gammadelta T lymphocytes in the peripheral blood of patients with tuberculosis with and without HIV co-infection

BACKGROUND: Several recent studies suggest that gammadelta T lymphocytes play an important role in immunity against Mycobacterium tuberculosis. However, the dynamics of these cells in the peripheral blood of patients with tuberculosis (TB) with and without HIV infection is not fully understood. A study was undertaken to evaluate the profile of the gammadelta T cell population in patients at the time the diagnosis of TB was established. METHODS: A cross sectional study was performed in consecutive TB patients from the Department of Infectious Diseases, Spedali Civili, Brescia. CD4+, CD8+ and Vdelta1 and Vdelta2 T cell counts were analysed. Lymphocyte surface membrane expression was evaluated with the FITC-TCRgammadelta, -Vdelta1, -Vdelta2 and PE-Vdelta1 monoclonal antibodies. Blood donors and HIV seropositive asymptomatic individuals acted as controls. RESULTS: Seventy four TB patients were evaluated, 20 of whom (27%) were co-infected with HIV. HIV seronegative TB patients (n=54) had total gammadelta T cells and Vdelta1 subsets comparable to those in blood donors (n=39). However, the percentage with the Vdelta2 subset was significantly lower in patients with TB than in controls (median 1.5 v 2.1; p=0.05). Responsiveness to PPD was not associated with predominance of a specific gammadelta T cell subset. HIV seropositive individuals had a decreased percentage of circulating Vdelta2 cells at a level similar to that in HIV seronegative TB patients, regardless of the presence of active TB. CONCLUSIONS: HIV seronegative TB patients and HIV infected individuals (with or without active TB) have a reduced number of circulating Vdelta2 T cells compared with healthy individuals. Whether TB and HIV infection share a common mechanism causing Vdelta2 T cell depletion still needs to be established.     

一期和二期髋关节翻修术后感染复发率的Meta分析

目的比较一期和二期翻修术治疗全髋关节置换术(THA)后感染的感染复发率。 方法在Pubmed、EMBase和Medline(1988年1月到2017年1月)3个数据库进行检索。收集THA术后感染行一期和二期翻修的文章。筛选符合预先设定标准(一期翻修与二期翻修对照治疗全髋关节置换术后感染,排除非对照研究)的文章,提取手术例数及感染复发例数进行Meta分析。采用Review Manager 5.3软件统计分析感染复发率。 结果初检1 084篇,最终纳入10篇。THA术后感染总共1 116例,其中一期翻修480例,二期翻修636例;一期和二期的感染复发率对比结果为[OR ＝ 1.40,95%CI(0.92,2.15),P ＝0.12]。如果将软组织情况良好、骨缺损少、致病菌明确且对药物敏感作为一期翻修的选择条件,一期和二期翻修的感染复发率相似,结果无统计学意义[OR＝0.44,95%CI(0.13,1.41),P ＝0.17];对于THA术后感染,如果不考虑软组织、骨缺损、致病菌的情况下行翻修手术,二期翻修的感染复发率比一期低,结果具有统计学意义[OR ＝1.79,95%CI(1.11,2.88),P ＝0.02]。 结论对于THA术后感染的治疗,局部条件良好与否会影响一期和二期翻修术后感染复发率。     

On the co‐infection of dengue fever and Zika virus

In this paper, we present a co‐infection mathematical model for dengue‐Zika disease in order to carry out their synergistic relationship in the presence of prevention and treatment. Submodel analysis is investigated to establish the reproduction numbers for each disease and to determine the disease‐free local stability equilibrium status. The endemic disease equilibrium is investigated using bifurcation analysis and shows backward bifurcation. We use Pontryagin's maximum principle to explore and determine the best optimal strategies to control both diseases. Numerical optimal control analysis indicates that effective prevention and treatment of each disease will help in the effective control and eradication of the diseases. Finally, the control of co‐infection of dengue‐Zika requires that communities should combine both prevention and treatment associated with each disease at the same time.     

Disseminated kidney tuberculosis complicating autosomal dominant polycystic kidney disease: a case report

Mycobacterium tuberculosis infection in patients with autosomal dominant polycystic kidney disease (ADPKD) is rare, and its diagnosis and treatment are difficult because numerous cysts are exposed to infection and antibiotics do not easily penetrate infected cysts. Here, we report the case of a 43-year-old Japanese man with disseminated urogenital tuberculosis (TB) and ADPKD without human immunodeficiency virus (HIV) infection. Delayed diagnosis and ineffective anti-TB chemotherapy worsened his condition. Finally, he underwent bilateral nephrectomy but experienced postoperative complications. In conclusion, kidney TB should be recognized as a cause of renal infection in ADPKD, and surgical treatment should be instituted without delay. The importance of early diagnosis and treatment cannot be overemphasized to prevent kidney TB deterioration.     

Tuberculosis--the patients' perspective

This, the last of three studies examining aspects of tuberculosis (TB) control in South Africa, ascertained the views of the consumer--the TB patient. Aspects such as the impact of contracting TB on employment opportunities and social life, difficulties in getting treatment, and knowledge of TB were studied in a sample population of urban black working-class TB patients. Patients had difficulties in getting treatment at centralized points, and health education was not effective. Poor socio-economic conditions were also important in the experience of the TB sufferer.     

Spondylitis tuberculosa der Halswirbelsäule

WHO estimates that worldwide more than 4 million people are infected with tuberculosis (TB), 95% of them living in third world countries. TB is once again the most frequent infectious disease [1, 2, 7]. Extrapulmonary forms (EPTB) frequently appear with HIV-associated TB [3, 4, 6]. We present the case of a 23-year old patient with abscess forming TB of the right apical lung with infiltration and partial osteolytical destruction of the 7th cervical- and the first thoracal vertebral body. Progressive spinal compression lead to partial sensomotorical deficits. Surgical revision of the abscess, an atypical resection of the right apical lung and right wing hemilaminectomy of Th1/2 for spinal decompression became necessary. The spinal stabilisation was achieved by conservative treatment for 6 weeks only by a Minerva cast and for another 8 weeks by a cervical stiffneck. Following mobilisation was without problems and the neurological deficits subsided within 3 months. Clinical examination and functional X-rays analysis proved vertebral stability and good function. The treatment of TB is basically conservative. Surgery is only recommended in case of functional and infectious complications.     

Recurrent carotid stenosis after autologous tissue patching

This study was carried out to evaluate two techniques of widening the carotid bifurcation with autologous material after endarterectomy to determine whether the incidence of recurrent stenosis could be reduced. As a control, a similar series was performed without patching. Autologous saphenous vein was used as a patch in one group of patients, whereas in another, the bifurcation was widened by suturing the external carotid to the internal carotid artery, advancing the bifurcation by several centimeters, a technique we termed bifurcation advancement. All three groups were studied at least 1 year after operation by means of Doppler ultrasonography. We found no difference in either of the patched techniques compared with unpatched controls. Significant recurrent stenosis (greater than 50% diameter reduction) was found in 12.5% of reconstructions with a vein patch, 12.5% of those with bifurcation advancement, and 16.6% of those with simple closure. The overall incidence of significant recurrent stenosis was 13.8%, with symptoms occurring in 2.7%.     

Transboundary tuberculosis: Importation of alpacas infected with Mycobacterium bovis from the United Kingdom to Poland and potential for serodiagnostic assays in detecting tuberculin skin test false‐negative animals

The present study highlights the transboundary nature of tuberculosis (TB) in alpacas and the failure of current antemortem testing protocols to identify TB‐free alpaca herds and individuals for exportation. The tuberculin skin test (TST) failed to identify Mycobacterium bovis‐infected animals prior to movement from the United Kingdom (UK) to Poland. This study describes the use of four serological assays [Enferplex Camelid TB, dual‐path platform (DPP) VetTB and BovidTB assays, and multi‐antigen print immunoassays (MAPIAs)] to detect TB in an alpaca herd with negative TST results. The breeding in Poland purchased alpacas for several years from the UK with the last group arriving in May 2018. In July 2018, two sick alpacas from the centre were hospitalized in a veterinary clinic and both died of TB a few weeks later. In November 2018, 20 alpacas remaining in this M. bovis‐affected herd were euthanized and samples were collected. The study population included 20 M. bovis‐infected and 20 uninfected alpacas, but only 15 infected animals were tested by all serology tests. The DPP VetTB and DPP BovidTB assays detected antibodies in 14 of the 20 infected alpacas, with results confirmed by MAPIA, and in none (MAPIA and DPP BovidTB) or one (DPP VetTB) of the 20 uninfected animals. None of the infected alpacas tested positive using the Enferplex assay. In addition, the group included three orphans and two cria–dam pairs, which provided an opportunity to analyse immune aspects of cria–mother relationships in this herd. The results suggest high susceptibility of this host species to M. bovis infection and rapid progression to disease. The serological tests used in this study offer useful tools for the detection of M. bovis infection in TST and Enferplex test non‐reactive alpacas. These tests should be further evaluated for implementation into TB management and control strategies for camelid species.     

Optimal control of HIV treatment and immunotherapy combination with state and control delays

In this paper, we propose and analyze an optimal control problem where human immunodeficiency virus treatment and immunotherapy are described by two control functions that are subject to time delays representing pharmacological and absorption delays, respectively. The goal is to propose effective optimal control solutions for the combination of human immunodeficiency virus treatment and immunotherapy, ensuring a functional behavior of the immune system. The incubation period is mathematically represented by a time delay in the virus load, and the local asymptotic and Hopf bifurcation analysis of the CTL-equilibrium point of the uncontrolled delayed system is studied. We obtain optimal controls of bang-singular type both for the nondelayed and delayed optimal control problem with and without state constraints. We study boundary arcs of state constraints and junction properties of the control and adjoint variables at entry and exit points of boundary arcs. Moreover, we derive an explicit formula of the multiplier associated with the state constraint.     

个性化制作骨水泥间隔器治疗人工全膝关节置换术后感染

目的探讨利用计算机辅助设计及三维打印技术制作个性化骨水泥间隔器治疗人工全膝关节置换（TKA）术后感染的临床疗效。方法自2010-03—2012-03,采用一期置入个性化制作的骨水泥间隔器、二期翻修重建术治疗8例TKA术后感染。结果所有患者均未发现与骨水泥间隔器相关的骨折、脱位及不稳定。2次手术间隔期为12~20周,平均15周。患者在间隔期均能扶拐行走,屈膝无明显受限,活动度90°~120°,平均100°。间隔期膝关节功能KSS评分平均81分。二期翻修术后随访12~24个月,平均15个月,未发现感染复发与新的感染。结论个性化制作的骨水泥间隔器与原假体取出后的腔隙完美匹配,并且能最大程度保留术后关节的活动度,治疗TKA术后感染疗效可靠。     

Optimal drug control in a four-dimensional HIV infection model

In this paper, we consider a four-dimensional version of a human immunodeficiency virus (HIV) infection model, which is an extension of some previous three-dimensional models. We approach the treatment problem by adding two controls u₁ and u₂ to the system for inhibiting viral production and preventing new infections. In fact, u₁ is added to components of uninfected and infected cells to represent the effect of chemotherapy on the interaction of uninfected CD4⁺ T cells with infected cells. u₂ is considered in the effector immune component as immunotherapy. The purpose of this work is to control the progress of the disease in a steady state. Hence, first, we obtain a relation between the two controls u₁ and u₂ such that a Hopf bifurcation occurs. Next, the Pontryagin minimum principle will be applied to derive the optimal therapy for HIV. At the end, numerical results are presented.     

Paradoxical reactions during tuberculosis treatment in patients with and without HIV co-infection

BACKGROUND: It has been suggested that deterioration of tuberculosis (TB) during appropriate treatment, termed a paradoxical reaction (PR), is more common and severe in HIV positive individuals on highly active antiretroviral therapy (HAART). METHOD: A study was undertaken to determine the frequency of PR and its associated features in a population of HIV+TB+ patients and a similar sized group of HIV-TB+ individuals. RESULTS: PR occurred in 28% of 50 HIV+TB+ patients and 10% of 50 HIV-TB+ patients. Disseminated TB was present in eight of 13 HIV+TB+ patients and four of five HIV-TB+ patients with PR. In 28 HIV+TB+ patients starting HAART, PR was significantly associated with commencing HAART within 6 weeks of starting antituberculosis treatment (p = 0.03) and was more common in those with disseminated TB (p = 0.09). No association was found between development of PR and baseline CD4 count or CD4 response to HAART. CONCLUSIONS: PR is common in HIV infected and uninfected individuals with TB. Early introduction of HAART and the presence of disseminated TB appear to be important in co-infected patients.     

Vancomycin-supplemented impacted bone allografts in infected hip arthroplasty. Two-stage revision results

Bone allografts can store and release high levels of vancomycin. We present our results of a two-stage treatment for infected hip arthroplasty with acetabular and femoral impaction grafting using vancomycin-loaded allografts. We treated 29 patients (30 hips) by removal of the implants, meticulous debridement, parenteral antibiotic therapy and second-stage reconstruction using vancomycin-supplemented impacted bone allografts and a standard, cemented Charnley femoral component. The mean follow-up was 32.4 months (24 to 60). Infection control was obtained in 29 cases (re-infection rate of 3.3%; 95% confidence interval 0.08 to 17) without evidence of progressive radiolucent lines, demarcation or graft resorption. One patient had a further infection ten months after revision caused by a different pathogen. Associated post-operative complications were one traumatic periprosthetic fracture at 14 months, a single dislocation in two hips and four displacements of the greater trochanter. Vancomycin-supplemented allografts restored bone stock and provided sound fixation with a low incidence of further infection.     

Mathematical modeling to design public health policies for Chikungunya epidemic using optimal control

In this article, we study the control of a Chikungunya epidemic model solving several optimal control problems. We implement three strategies to control the spread of the Chikungunya virus in the human and vector population. The first control strategy is an educational campaign promoting the use bednets, avoiding water stagnation, wearing long sleeved shirts, among others. The second is treatment of the infected individual, and the third relies on spraying insecticide. The optimal control problem that we solve has a mathematical model for Chikungunya representing the control system. We rely on Pontryagin's maximum principle to solve the optimal control problem. For the mathematical model of the Chikungunya epidemic, we use the incidence data from Colombia corresponding to the year 2015. An additional aim of this study is to investigate which control measures are more efficient and suggest policies to health institutions to reduce the number of infected individuals. Although the mathematical model fits real data of the Colombian case, the policies and insights presented in this article might be extrapolated to different countries.     

Reducing joint destruction due to septic arthrosis using an adenosine2A receptor agonist.

We assessed the efficacy of a new adenosine A2A agonist ATL146e, a potent inhibitor of white blood cell chemotaxis, to reduce cartilage damage in the treatment of septic arthrosis. A live septic arthrosis model was created using Staphylococcus aureus in rabbit knees. Animals were divided into five treatment groups: (1) untreated infected control, (2) antibiotics control, and antibiotics plus ATL146e for (3) 24, (4) 48, or (5) 72 h and assessed at 1, 4, and 7 days. Knees in all ATL146e treated animals exhibited no detectable effusion, and histologic examination revealed near normal cartilage and diminished synovial inflammatory response. Synovial WBC counts decreased with the addition of ATL146e when compared to infected and antibiotic controls. Histologic grading of osteochondral specimens demonstrated improved scores for animals treated with ATL146e compared to infected (p<0.00004) and antibiotics controls (p<0.05). Analysis of glycosaminoglycan content revealed significantly decreased loss of articular cartilage following infection in the ATL146e groups when compared to infected (p<0.03) and antibiotics controls (p<0.05). Addition of an adenosine A2A agonist to antibiotic therapy decreases joint inflammation and articular cartilage destruction without compromising bacterial clearance in rabbit knees following intraarticular bacterial infection. The use of adenosine agonists selective to the A2A receptor to augment conventional treatment of joint sepsis may be chondroprotective and ultimately help prevent arthrosis.     

Pharmacokinetics and degree of aromatization rather than total dose of different preparations determine the effects of testosterone: a nonhuman primate study in Macaca fascicularis

Currently available testosterone (T) preparations differ substantially in their pharmacokinetic profile that might influence their androgenic properties in terms of suppression of the gonadal axis, effects on anabolic parameters, lipid metabolism, and erythropoiesis. The present work was undertaken to determine the physiological effects of three T preparations with different serum kinetics. Twenty adult male cynomolgus monkeys (Macaca fascicularis) were randomly assigned to receive treatment for 28 weeks with either T enanthate (TE) every 4 weeks, T buciclate (TB) every 7 weeks, or T undecanoate (TU) every 10 weeks or remaining untreated (controls). Each injection delivered 20 mg pure T per kilogram body weight. Pharmacokinetic profiles demonstrated higher peak levels of T for TE-treated animals; serum half-lives were longer for TU or TB. Estradiol levels (area under the curve) were significantly higher in TB vs TU or TE. All T regimens suppressed serum luteinizing hormone bioactivity and testicular volumes declined (all P <.001 vs controls). Sperm counts were markedly lowered in all animals but least in TE (P <.01 vs TB or TU). During recovery phase, return to normal for all three parameters occurred significantly earlier in TE-treated animals, followed by those given TU, compared with TB (all P <.001 between groups). Body weight increased significantly during T exposure. This effect was stronger and more sustained in TB vs TU or TE (both P <.001). Serum creatinine and hemoglobin increased with high significance in all T-treated animals (all P <.001 vs controls). The lowering impact of T on serum lipids was markedly stronger in the longer-acting T preparations in comparison with TE, as were effects on purine metabolism (all P <.001). The pattern of exposure and degree of aromatization rather than overall exposure to T determine its effects in the preclinical primate model. Both fluctuations of androgen concentrations and the conversion rate to estradiol influence gonadal suppression as well as metabolism. These results have to be considered in men receiving treatment for hypogonadism or regimens for hormonal contraception.     

Optimal control of a delayed hepatitis B viral infection model with HBV DNA‐containing capsids and CTL immune response

This paper deals with an optimal control problem of a time‐delayed differential equation model that describes the interactions between hepatitis B virus (HBV) with HBV DNA‐containing capsids, liver cells (hepatocytes), and cytotoxic T‐lymphocyte immune response. Both the treatment and the intracellular delay are incorporated into the model. Furthermore, the existence of the optimal control pair is studied, and Pontryagin's minimum principle is used to characterize these 2 optimal controls. The first of them represents the efficiency of drug treatment in preventing new infections, whereas the second stands for the efficiency of drug treatment in inhibiting viral production. The optimality system is derived and solved numerically using the forward and backward difference approximation. Finally, numerical simulations are established to show the role of optimal therapy in controlling viral replication.