Intravitreal bevacizumab: an analysis of the evidence

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Polymerase chain reaction to search for Herpes viruses in uveitic and healthy eyes: a South African perspective

Objective: To analyse aqueous polymerase chain reaction (PCR) results in patients diagnosed with undifferentiated uveitis and determine prevalence of herpesviridae in non-uveitic patients undergoing routine cataract extraction. Design: Retrospective comparative case series and prospective cross-sectional study. Subjects: 72 patients with idiopathic uveitis and 57 surgical patients. Methods: Diagnostic aqueous paracentesis with PCR testing for 6 herpes viridae in uveitic patients. Anterior chamber paracentesis immediately pre-operative in the prospective arm, with PCR testing. Results: In the retrospective review we had a 47.2% positive PCR yield. Data analysis revealed a statistically significant correlation between a positive yield and being HIV+ (p=0.018); between an EBV+ yield and being HIV+ (p= 0.026) and a CMV+ result and being HIV+ (p=0.032). Posterior uveitis (p=0.014) and symptoms <30 days (p= 0.0014) had a statistically significant yield. In the prospective arm of the study: all 57 patients were HIV- and all aqueous samples were negative for the 6 herpesviridae. Conclusion: We recommend PCR testing for Herpesviridae as a safe second line test for patients with undifferentiated uveitis. We were unable to establish prevalence and suggest that the idea of a commensal herpes virus is unlikely if the blood-ocular barrier is intact

Streptococcus pneumoniae Serotype-2 Childhood Meningitis in Bangladesh: A Newly Recognized Pneumococcal Infection Threat

BACKGROUND: Streptococcus pneumoniae is a leading cause of meningitis in countries where pneumococcal conjugate vaccines (PCV) targeting commonly occurring serotypes are not routinely used. However, effectiveness of PCV would be jeopardized by emergence of invasive pneumococcal diseases (IPD) caused by serotypes which are not included in PCV. Systematic hospital based surveillance in Bangladesh was established and progressively improved to determine the pathogens causing childhood sepsis and meningitis. This also provided the foundation for determining the spectrum of serotypes causing IPD. This article reports an unprecedented upsurge of serotype 2, an uncommon pneumococcal serotype, without any known intervention. METHODS AND FINDINGS: Cases with suspected IPD had blood or cerebrospinal fluid (CSF) collected from the beginning of 2001 till 2009. Pneumococcal serotypes were determined by capsular swelling of isolates or PCR of culture-negative CSF specimens. Multicenter national surveillance, expanded from 2004, identified 45,437 patients with suspected bacteremia who were blood cultured and 10,618 suspected meningitis cases who had a lumber puncture. Pneumococcus accounted for 230 culture positive cases of meningitis in children <5 years. Serotype-2 was the leading cause of pneumococcal meningitis, accounting for 20.4% (45/221; 95% CI 15%-26%) of cases. Ninety eight percent (45/46) of these serotype-2 strains were isolated from meningitis cases, yielding the highest serotype-specific odds ratio for meningitis (29.6; 95% CI 3.4-256.3). The serotype-2 strains had three closely related pulsed field gel electrophoresis types. CONCLUSIONS: S. pneumoniae serotype-2 was found to possess an unusually high potential for causing meningitis and was the leading serotype-specific cause of childhood meningitis in Bangladesh over the past decade. Persisting disease occurrence or progressive spread would represent a major potential infection threat since serotype-2 is not included in PCVs currently licensed or under development

How Can the Operating Environment for Nutrition Research Be Improved in Sub-Saharan Africa? The Views of African Researchers

Optimal nutrition is critical for human development and economic growth. Sub-Saharan Africa is facing high levels of food insecurity and only few sub-Saharan African countries are on track to eradicate extreme poverty and hunger by 2015. Effective research capacity is crucial for addressing emerging challenges and designing appropriate mitigation strategies in sub-Saharan Africa. A clear understanding of the operating environment for nutrition research in sub-Saharan Africa is a much needed prerequisite. We collected data on the barriers and requirements for conducting nutrition research in sub-Saharan Africa through semi-structured interviews with 144 participants involved in nutrition research in 35 countries in sub-Saharan Africa. A total of 133 interviews were retained for coding. The main barriers identified for effective nutrition research were the lack of funding due to poor recognition by policymakers of the importance of nutrition research and under-utilisation of research findings for developing policy, as well as an absence of research priority setting from within Africa. Current research topics were perceived to be mainly determined by funding bodies from outside Africa. Nutrition researchers argued for more commitment from policymakers at national level. The low capacity for nutrition research was mainly seen as a consequence of insufficient numbers of nutrition researchers, limited skills and a poor research infrastructure. In conclusion, African nutrition researchers argued how research priorities need to be identified by African stakeholders, accompanied by consensus building to enable creating a problem-driven national research agenda. In addition, it was considered necessary to promote interactions among researchers, and between researchers and policymakers. Multidisciplinary research and international and cross-African collaboration were seen as crucial to build capacity in sub-Saharan nutrition research

New approaches in the diagnosis and treatment of latent tuberculosis infection

With nearly 9 million new active disease cases and 2 million deaths occurring worldwide every year, tuberculosis continues to remain a major public health problem. Exposure to Mycobacterium tuberculosis leads to active disease in only ~10% people. An effective immune response in remaining individuals stops M. tuberculosis multiplication. However, the pathogen is completely eradicated in ~10% people while others only succeed in containment of infection as some bacilli escape killing and remain in non-replicating (dormant) state (latent tuberculosis infection) in old lesions. The dormant bacilli can resuscitate and cause active disease if a disruption of immune response occurs. Nearly one-third of world population is latently infected with M. tuberculosis and 5%-10% of infected individuals will develop active disease during their life time. However, the risk of developing active disease is greatly increased (5%-15% every year and ~50% over lifetime) by human immunodeficiency virus-coinfection. While active transmission is a significant contributor of active disease cases in high tuberculosis burden countries, most active disease cases in low tuberculosis incidence countries arise from this pool of latently infected individuals. A positive tuberculin skin test or a more recent and specific interferon-gamma release assay in a person without overt signs of active disease indicates latent tuberculosis infection. Two commercial interferon-gamma release assays, QFT-G-IT and T-SPOT.TB have been developed. The standard treatment for latent tuberculosis infection is daily therapy with isoniazid for nine months. Other options include therapy with rifampicin for 4 months or isoniazid + rifampicin for 3 months or rifampicin + pyrazinamide for 2 months or isoniazid + rifapentine for 3 months. Identification of latently infected individuals and their treatment has lowered tuberculosis incidence in rich, advanced countries. Similar approaches also hold great promise for other countries with low-intermediate rates of tuberculosis incidence

Anti-infective ophthalmic preparations in general practice

CITATION: Smit, D. 2012. Anti-infective ophthalmic preparations in general practice. South African Family Practice, 54(4):302-307.The original publication is available at http://www.safpj.co.zaOcular infections may be bacterial, viral, fungal or parasitic in aetiology. Pharmacological preparations are available to treat infections that are caused by these groups of organisms. The majority of these preparations are intended for topical administration, although some systemically administered agents may be needed to treat or prevent specific ocular infections. This article discusses the different anti-infective options that are available to general practitioners to treat infections caused by each aetiological group. It also discusses the role that is played by povidone-iodine and antibiotic-steroid combinations to manage eye infections. A summary of all these drugs is provided in table form for easy reference.http://www.safpj.co.za/index.php/safpj/article/view/3598Publisher's versio

Dealing with dry eye disease in general practice

CITATION: Smith, D. 2012. Dealing with dry eye disease in general practice. South African Family Practice, 54(1):14-18.The original publication is available at http://www.safpj.co.zaDry eye disease (DED) is a very common condition with significant morbitity. It is under-diagnosed by healthcare practitioners, since the presenting symptoms are often non-specific or misleading, and clinical signs may be subtle, or absent. To help overcome this problem, validated symptom questionnaires have been developed to aid the diagnosis, and grading of severity, of DED. Recent advances in the understanding of the multifactorial aetiology of this condition have also permitted the development of modalities aimed at treating specific underlying causes, rather than merely alleviating symptoms. An awareness of the causes and risk factors involved in this disease will assist the family practitioner in recommending lifestyle and dietary changes that, on their own, may provide sufferers with considerable symptomatic relief. A better understanding of the pathophysiology will, in turn, allow the family practitioner to make informed choices when prescribing initial treatment, and also guide the practitioner to know when to refer a patient for specialist management.http://www.safpj.co.za/index.php/safpj/article/view/2083Publisher's versio

Eyelid problems in general practice

CITATION: Smit, D. P. 2012. Eyelid problems in general practice. South African Family Practice, 54(3):214-220.The original publication is available at http://www.safpj.co.zaGeneral practitioners are often confronted with complaints regarding the eyelids. The author presents a number of clinical cases that illustrate common eyelid problems, and provides a discussion of each case to highlight the important features of the condition. Appropriate treatment for each condition is also covered. Many eyelid conditions are amenable to treatment from general practitioners, but those conditions requiring specialist management need to be identified, and referred appropriately.http://www.safpj.co.za/index.php/safpj/article/view/1755Publisher's versio

An investigation into the causes of intraocular inflammation in HIV-positive and HIV-negative patients in the Western Cape Province, South Africa

Thesis (PhD (Surgical Sciences. Ophthalmology))--Stellenbosch University, 2018.ENGLISH SUMMARY: The causes of intraocular inflammation are divided into 3 large groups namely infectious, non-infectious and idiopathic. This research project set out to establish the prevalence of these 3 large groups and their different subgroups in an effort to determine whether HIV infection plays an important role in how frequently they occur in the Western Cape Province. Out of a total of 106 participants with uveitis enrolled in this study, 66 cases (62.3%) were HIV- and 40 (37.7%) HIV+ with a median CD4+ cell count of 242 x 106/l. The majority of participants were black (n=52; 49.1%) or of mixed ethnicity (n=49; 46.2%) and 59.6% of blacks were HIV+ versus 16.3% of mixed ethnicity participants. Anatomically, most cases were either anterior uveitis (58.5%) or panuveitis (32.1%) while infectious uveitis (n=70; 66.0%) was more common than non-infectious (n=18; 17.0%) or idiopathic (n=18; 17.0%) uveitis. An infectious cause was found in 80.0% of HIV+ cases versus 57.6% in HIV- cases. Intraocular tuberculosis (IOTB) was the most common cause of infectious uveitis in this study (n=35; 33.0%) where possible IOTB (n=23; 21.7%) was more common than probable IOTB (n=12; 11.3%). Tuberculin skin testing alone was more sensitive (90.3% vs 85.7%) and had a higher negative predictive value (92.1% vs 81.5%) than QuantiFERON alone and the latter therefore does not warrant the extra expense in our highly endemic setting. Herpetic uveitis formed the second largest group (n=13; 12.2%) with VZV (53.8%) responsible for more cases than CMV (38.5%) and HSV (7.7%). Syphilis was the third most common cause of infectious uveitis (n=11; 10.4%). Using a novel immunoblot approach the study investigated the relationship between ocular and neurosyphilis and demonstrated that these 2 conditions do not always co-exist. HIV infection was present in 31.4% of IOTB cases, 61.5% of herpetic cases and 81.8% of syphilitic cases. Toxoplasma (n=4; 3.8%), Rubella virus and poststreptococcal uveitis (n=3; 2.8% each) as well as HIV-induced uveitis (n=1; 0.9%) were responsible for the remainder of the infectious uveitis cases. EBV was often identified on multiplex PCR (n=11; 10.4%) but no evidence of active intraocular replication or antibody production was found to prove that EBV caused uveitis in these cases. In most cases an alternative treatable cause of uveitis was identified (n=9; 81.8%). Sarcoidosis and HLA-B27 associated anterior uveitis (n=8; 7.5% each) were the most common causes of non-infectious uveitis. All patients with ocular sarcoid and 75% of patients with HLA-B27 uveitis were HIV-. The percentage of idiopathic cases in this study was lower than in many similar studies (n=18; 17.0%). This is likely due to the high percentage of cases of possible IOTB diagnosed using a recently proposed classification as many of those cases would have been labelled as idiopathic in other studies. The majority of idiopathic uveitis cases were HIV- (n=12; 66.7%). This study revealed that infectious uveitis is the commonest form of uveitis in both HIV+ and HIV- patients but that the specific pathogens differ between patients with and without HIV infection.AFRIKAANSE OPSOMMING: Die oorsake van intraokulêre inflammasie word verdeel in 3 groot groepe naamlik infektief, non-infektief en idiopaties. Die doel van hierdie navorsingsprojek was om die prevalensie van hierdie 3 groepe asook hulle onderskeie subgroepe te bereken om te bepaal of HIV infeksie ‘n belangrike rol speel in hoe dikwels hulle in die Wes-Kaap provinsie voorkom. Uit ‘n totaal van 106 deelnemers aan hierdie studie was 66 gevalle (62.3%) HIV+ and 40 (37.7%) HIV- met ‘n mediane CD4+ seltelling van 242 x 106/l. Die meerderheid deelnemers was swart (n=52; 49.1%) of van gemengde etniese afkoms (n=49; 46.2%) en 59.6% van swart deelnemers was HIV+ teenoor 16.3% van deelnemers van gemengde afkoms. Anatomies was die meeste gevalle anterior uveitis (58.5%) of panuveitis (32.1%) terwyl infektiewe uveitis (n=70; 66.0%) meer algemeen was as non-infektiewe (n=18; 17.0%) of idiopatiese (n=18; 17.0%) uveitis. ‘n Infektiewe oorsaak is gevind in 80.0% van HIV+ gevalle teenoor 57.6% in HIV- gevalle. Intraokulêre tuberkulose (IOTB) was die algemeenste oorsaak van infektiewe uveitis in hierdie studie (n=35; 33.0%) waar moontlike IOTB (n=23; 21.7%) meer algemeen was as waarskynlike IOTB (n=12; 11.3%). ‘n Tuberkulien veltoets alleen was meer sensitief (90.3% vs 85.7%) en het ook ‘n hoër negatiewe voorspellende waarde (92.1% vs 81.5%) gehad as QuantiFERON alleen en laasgenoemde regverdig dus nie die addisionele finansiële uitgawe in hierdie hoogs endemiese gebied nie. Herpetiese uveitis was die tweede grootste groep (n=13; 12.2%) met VZV (53.8%) verantwoordelik vir meer gevalle as CMV (38.5%) en HSV (7.7%). Sifilis was die derde algemeenste oorsaak van infektiewe uveitis (n=11; 10.4%). Met behulp van ‘n nuwe immunoblot benadering is daar ondersoek ingestel na die verwantskap tussen okulêre sifilis en neurosifilis en is bewys dat dié 2 toestande nie altyd saam voorkom nie. HIV infeksie was teenwoordig in 31.4% van IOTB gevalle, 61.5% van herpetiese gevalle en 81.8% van sifilis gevalle. Toksoplasma (n=4; 3.8%), rubella-virus en poststreptokokkale uveitis (n=3; 2.8% elk) asook HIV-geinduseerde uveitis (n=1; 0.9%) was verantwoordelik vir die oorblywende infektiewe uveitis gevalle. EBV was dikwels teenwoordig op multipleks PKR (n=11; 10.4%) maar ons kon geen bewyse vind van aktiewe intraokulêre replikasie of teenliggaam produksie nie wat sou bewys dat EBV uveitis in hierdie gevalle veroorsaak het nie. In meeste gevalle is ‘n alternatiewe behandelbare oorsaak gevind (n=9; 81.8%). Sarkoiedose en HLA-B27 geassosieerde anterior uveitis (n=8; 7.5% elk) was die algemeenste oorsake van non-infektiewe uveitis. Al die pasiënte met okulêre sarkoiedose en 75% van pasiënte met HLA-B27 uveitis was HIV-. Die persentasie idiopatiese gevalle in hierdie studie was laer as in baie soortgelyke studies (n=18; 17.0%). Dit is waarskynlik as gevolg van die hoë persentasie gevalle met moontlike IOTB wat gediagnoseer is met ‘n onlangs gepubliseerde klassifikasie aangesien baie van daardie gevalle in ander studies as idiopaties beskou sou word. Die meerderheid idiopatiese gevalle was HIV- (n=12; 66.7%). Hierdie studie toon dat infektiewe uveitis algemeenste vorm van uveitis is in beide HIV+ en HIV- pasiënte maar dat die spesifieke patogene verskil tussen pasiënte met en sonder HIV infeksie

Pharmacologic testing in Horner's syndrome – a new paradigm

For more than three decades, topical cocaine has been used to confirm the diagnosis and hydroxyamphetamine to localise the causative lesion in oculosympathetic palsy or Horner’s syndrome. More recently, other drugs have demonstrated the ability to point to the diagnosis or anatomical site. Apraclonidine and phenylephrine, given their similar diagnostic efficacy and increased availability, may have superseded cocaine and hydroxyamphetamine as first-line pharmacological testing agents in Horner’s syndrome