Current World Health Organization Guidelines Research Articles

Changes in dietary intake and food sources of saturated and cis and trans unsaturated fatty acids in Costa Rican adolescents: 1996 versus 2006

ObjectiveTo identify how dietary intake and food sources of saturated (SFA) and cis (PUFA) and trans (TFA) unsaturated fatty acids in the diet of Costa Rican adolescents changed from 1996 to 2006—a period with several public health nutrition changes. MethodsCross-sectional comparisons used data from measured food records of 133 adolescents (ages 12–17 y) surveyed in 1996 and a similar group of adolescents surveyed in 2006. Values obtained in 1996 and 2006 were compared with the current World Health Organization guidelines for chronic disease prevention. ResultsAdolescents surveyed in 2006 reported a significantly higher mean daily energy intake from linoleic acid (LA) and alpha-linolenic acid (ALA) (0.9% and 7.8%, respectively) compared with the 1996 cohort, whereas SFA and TFA were significantly lower (9.5% and 1.3%, respectively). Food sources of fat also changed. In 2006, 2% of SFA in the diet came from palm shortening (compared with 34% in 1996); 39% of TFA came from ruminant-derived foods (in 1996, soybean oil was the main contributor of TFA, 34%), and bakery products (mainly pre-packaged cookies) provided 25% of the source of TFA, compared with only 11% in 1996. Dietary fatty intake of Costa Rican adolescents in 2006 is closer to WHO guidelines compared with 1996. ConclusionsAfter public health initiatives that changed fatty acid profile of most foods, intakes of TFA, SFA, and food sources of fatty acids in adolescents’ diets improved. Public health nutrition efforts should continue to strengthen diets that are low in SFA and TFA and higher in ALA content among Costa Rican adolescents.

Overdiagnosis of and treatment initiation delay in smear-negative pulmonary tuberculosis patients.

In this issue of Public Health Action, Viney et al. report on the frequency of and time to diagnosis in smear-negative pulmonary tuberculosis (PTB) patients in two Micronesian Island countries.1 The study participants were TB patients notified in the National TB Programme in Kiribati and the Marshall Islands for the period 2006–2010. The high percentage (42%) of smear-negative PTB cases highlighted two issues: 1) the possible overdiagnosis of smear-negative PTB, and 2) treatment initiation delay in smear-negative patients. TB diagnosis in these countries is based on the 2003 World Health Organization (WHO) guidelines,2 whereby individuals with presumptive TB submit three sputum samples for smear examination. In 326 (46%) smear-negative cases these guidelines were followed, but the diagnostic algorithm did not include culture or molecular techniques for Mycobacterium tuberculosis confirmation, and patients were referred for chest X-ray and/or clinical diagnosis. This may have led to an overdiagnosis of smear-negative PTB, and could account for the higher than expected proportion of cases (42% instead of 35%). As these are both lower-middle-income countries, newer diagnostic techniques to improve smear-negative diagnosis may be suggested.3 If, however, the cases do not undergo sufficient sputum investigations, as was shown in the study, it is imperative to address the programmatic challenges first. In addition, if current WHO guidelines were followed (i.e., testing of two sputum samples instead of three),4 58% instead of 46% of the study participants would have had diagnoses that concurred with the guidelines, which might be easier for both health care workers and patients to comply with. Zachary et al. recently reported a decrease in treatment initiation delay in smear-negative patients after the introduction of a digital X-ray facility.5 Such innovative measures could be evaluated in Micronesia, especially with the dependence on radiological and clinical diagnoses for smear-negative PTB. In the study reported here, 238 (34%) smear-negative cases were registered before smear examinations were done, and 131 (18%) were registered within 7 days of the first sputum smear investigation. However, in 234 (33%), the cause of the treatment initiation delay is not known. It would be interesting to investigate other aspects of health systems delay, such as diagnostic delay,6 focusing for example on the turnaround time of smear results, especially given that the TB services are centralised. Although smear-negative TB is associated with HIV (human immunodeficiency virus) infection,7 TB-HIV co-infection is extremely rare in the study countries, with no cases reported in 2010. Additional efforts should therefore focus on screening diabetic patients for TB, as diabetes has an excessively high prevalence in both countries. However, the association between smear-negative PTB and diabetes has not been made definitively, and subsequent research efforts are needed. The DOTS strategy was adopted in both countries in 2000, but the data do not suggest that presumptive TB cases are sufficiently investigated as per guidelines before being diagnosed with smear-negative PTB. Strengthening the TB programme to ensure that an increased proportion of cases undergo smear microscopy before registration, and accurate reporting of initiation of treatment, should be priorities.

The need for a reassessment of the safe upper limit of selenium in drinking water

Results of recent epidemiologic studies suggest the need to reassess the safe upper limit in drinking water of selenium, a metalloid with both toxicological and nutritional properties. Observational and experimental human studies on health effects of organic selenium compounds consumed through diet or supplements, and of inorganic selenium consumed through drinking water, have shown that human toxicity may occur at much lower levels than previously surmised. Evidence indicates that the chemical form of selenium strongly influences its toxicity, and that its biological activity may differ in different species, emphasizing the importance of the few human studies on health effects of the specific selenium compounds found in drinking water. Epidemiologic studies that investigated the effects of selenate, an inorganic selenium species commonly found in drinking water, together with evidence of toxicity of inorganic selenium at low levels in from in vitro and animal studies, indicate that health risks may occur at exposures below the current European Union and World Health Organization upper limit and guideline of 10 and 40μg/l, respectively, and suggest reduction to 1μg/l in order to adequately protect human health. Although few drinking waters are currently known to have selenium concentrations exceeding this level, the public health importance of this issue should not be overlooked, and further epidemiologic research is critically needed in this area.

Projecting the Long-Term Impact of School- or Community-Based Mass-Treatment Interventions for Control of Schistosoma Infection

BackgroundSchistosomiasis remains a significant health burden in many areas of the world. Morbidity control, focused on limiting infection intensity through periodic delivery of anti-schistosomal medicines, is the thrust of current World Health Organization guidelines (2006) for reduction of Schistosoma-related disease. A new appreciation of the lifetime impact of repeated Schistosoma infection has directed attention toward strategies for greater suppression of parasite infection per se, with the goal of transmission interruption. Variations in drug schedules involving increased population coverage and/or treatment frequency are now undergoing field trials. However, their relative effectiveness in long-term infection suppression is presently unknown.Methodology/Principal FindingsOur study used available field data to calibrate advanced network models of village-level Schistosoma transmission to project outcomes of six different community- or school age-based programs, as compared to the impact of current 2006 W.H.O. recommended control strategies. We then scored the number of years each of 10 typical villages would remain below 10% infection prevalence (a practicable level associated with minimal prevalence of disease). All strategies that included four annual treatments effectively reduced community prevalence to less than 10%, while programs having yearly gaps (‘holidays’) failed to reach this objective in half of the communities. Effective post-program suppression of infection prevalence persisted in half of the 10 villages for 7–10 years, whereas in five high-risk villages, program effects on prevalence lasted zero to four years only.Conclusions/SignificanceAt typical levels of treatment adherence (60 to 70%), current WHO recommendations will likely not achieve effective suppression of Schistosoma prevalence unless implemented for ≥6 years. Following more aggressive 4 year annual intervention, some communities may be able to continue without further intervention for 8–10 years, while in higher-risk communities, annual treatment may prove necessary until eco-social factors fostering transmission are removed. Effective ongoing surveillance and locally targeted annual intervention must then become their mainstays of control.

Should Sputum Smear Examination Be Carried Out at the End of the Intensive Phase and End of Treatment in Sputum Smear Negative Pulmonary TB Patients?

BackgroundThe Indian guidelines on following up sputum smear-negative Pulmonary tuberculosis (PTB) patients differ from the current World Health Organization (WHO) guidelines in that the former recommends two follow up sputum examinations (once at the end of intensive phase and the other at the end of treatment) while the latter recommends only one follow up sputum smear microscopy examination, which is done at the end of the intensive phase. This study was conducted to examine if there was any added value in performing an additional sputum smear examination at the end of treatment within the context of a national TB program.MethodsThis study was a descriptive record based review conducted in nine tuberculosis (TB) units in Delhi, India. All consecutive new sputum smear-negative PTB patients registered in these nine TB units from 1st January 2009 to 31st December 2009 were included in the study.ResultsOf 2567 new sputum smear-negative TB patients, 1973 (90%) had sputum specimens examined at the end of the intensive phase, of whom 36 (2%) were smear-positive: the majority (n = 28) successfully completed treatment with either the same or a re-treatment regimen. At treatment completion, 1766 (85%) patients had sputum specimens examined, of whom 16 (0.9%) were smear-positive: all these were changed to a re-treatment regimen. Amongst the sputum-positive patients identified as a result of follow up (n = 52), four were diagnosed with multi-drug resistant TB (MDR-TB), three of whom were detected after smear examination at the end of treatment.ConclusionsGiven the high burden of TB in India, a 0.9% additional yield of smear-positive sputum smears at the end of treatment translates to 3,297 cases of smear-positive PTB. End-of-treatment smear is a low-yield strategy for detection of smear-positive TB cases, although further studies are needed to determine its population-level impact and cost, particularly in relation to other TB control interventions.

Household Costs for Treatment of Severe Pneumonia in Pakistan

Current World Health Organization (WHO) guidelines for severe pneumonia treatment of under-5 children recommend hospital referral. However, high treatment cost is a major barrier for communities. We compared household costs for referred cases with management by lady health workers (LHWs) using oral antibiotics. This study was nested within a cluster randomized trial in Haripur, Pakistan. Data on direct and indirect costs were collected through interviews and record reviews in the 14 intervention and 14 control clusters. The average household cost/case for a LHW managed case was $1.46 compared with $7.60 for referred cases. When the cost of antibiotics provided by the LHW program was excluded from the estimates, the cost/case came to $0.25 and $7.51 for the community managed and referred cases, respectively, a 30-fold difference. Expanding severe pneumonia treatment with oral amoxicillin to community level could significantly reduce household costs and improve access to the underprivileged population, preventing many child deaths.

An in silico drug treatment model to assess the robustness of regional age-based dosing regimens for artemisinin-based combination therapies

The standard drug development process for antimalarials and other drugs uses weight-based dosing (mg/kg) to predict blood concentrations of the drug, and hence their effect. Consequently, the current World Health Organization Guidelines for the treatment of malaria [1] provide target doses and therapeutic dose ranges in mg/ kg/day. However, in resource-poor settings, age-based dosing is often employed instead of weight-based dosing because of the scarcity of correctly functioning weighing scales outside of clinical settings. Due to the wide variation in weight by age this approach inevitably results in over- and under-dosing of a proportion of the population. We have recently developed a modelling method to create statistically robust global and regional malaria-specific weight-for-age references representative of the malaria-endemic countries [2] and employed it to predict optimized age-based regimens for artemisinin-based combination therapies (ACTs) for case management of uncomplicated malaria (unpublished). The presented work now assesses the robustness of these age-based regimens using an in silico model of antimalarial drug treatment to predict treatment outcome based on individual infection parameters such as parasite numbers, variation in patient pharmacokinetics, and parasite variation in their drug sensitivity [3]. This extended pharmacokinetic/pharmakodynamic model for ACTs allowed us to investigate extreme treatment scenarios in a large number of patients over long follow-up periods that for ethical reasons could not be applied in clinical trials: typical examples include poor adherence (e.g. delayed, reduced or missed doses) or administration of doses above or below recommended therapeutic dose ranges and particularly in most vulnerable individuals such as infants and young children. Pharmacological modelling of antimalarial treatment cannot replace the gold standard of clinical trials, but the model outputs can identify patient groups that are at higher risk of treatment failure due to under-dosing or adverse events due to over-dosing. We acknowledge the Medical Research Council for funding of this work.

Effect of injectable contraceptive use on response to antiretroviral therapy among women in Rakai, Uganda

BackgroundThere is limited evidence on the effect of injectable contraception on response to antiretroviral therapy (ART). DesignUsing modified Poisson regression, we assessed data from 418 female Ugandan ART initiators to examine the effect of injectable contraceptive use on a composite virologic failure outcome (defined as failure to achieve virologic suppression, switch to second line therapy, or death within 12 months of ART initiation) and also assessed ART adherence. ResultsAbout 12% of women reported using injectable contraceptives at ART initiation, and their composite virologic failure rates 12 months later were similar to women not using injectable contraceptives at ART initiation (11% vs. 12%, p=0.99). Multivariable Poisson regression suggested no significant differences in virologic failure by injectable contraceptive use at baseline (prevalence risk ratio: 0.85, p=0.71), but power was limited. Adherence to ART increased with time since ART initiation, and did not appear to differ between injectable contraceptive users and non-users. ConclusionsConsistent with current World Health Organization guidelines, our results suggest no deleterious effect of injectable contraceptive use on response to ART, but power was limited, injectable contraceptive use patterns over time were inconsistent and additional evidence is needed.

Cytochrome c biosensor for determination of trace levels of cyanide and arsenic compounds

An electrochemical method based on a cytochrome c biosensor was developed, for the detection of selected arsenic and cyanide compounds. Boron doped diamond (BDD) electrode was used as a transducer, onto which cytochrome c was immobilised and used for direct determination of Prussian blue, potassium cyanide and arsenic trioxide. The sensitivity as calculated from cyclic voltammetry (CV) and square wave voltammetry (SWV), for each analyte in phosphate buffer (pH=7) was found to be in the range of (1.1–4.5)×10−8AμM−1 and the detection limits ranged from 4.3 to 9.1μM. The biosensor is therefore able to measure significantly lower than current Environmental Protection Agency (EPA) and World Health Organisation (WHO) guidelines, for these types of analytes. The protein binding was monitored as a decrease in biosensor peak currents by SWV and as an increase in biosensor charge transfer resistance by electrochemical impedance spectroscopy (EIS). EIS provided evidence that the electrocatalytic advantage of BDD electrode was not lost upon immobilisation of cytochrome c. The interfacial kinetics of the biosensor was modelled as equivalent electrical circuit based on electrochemical impedance spectroscopy data. UV–vis spectroscopy was used to confirm the binding of the protein in solution by monitoring the intensity of the soret bands and the Q bands. FTIR was used to characterise the protein in the immobilised state and to confirm that the protein was not denatured upon binding to the pre-treated bare BDD electrode. SNFTIR of cyt c immobilised at platinum electrode, was used to study the effect of oxidation state on the surface bond vibrations. The spherical morphology of the immobilised protein, which is typical of native cytochrome c, was observed using scanning electron microscopy (SEM) and confirmed the immobilisation of the cytochrome c without denaturisation.

Yet Another Reason to Treat HIV Infection

Antiretroviral therapy (ART) has allowed a cohort of children who were perinatally infected with human immunodeficiency virus (HIV) to reach early adulthood, but their risk of death, non-AIDS-defining infections, cancers and organ failure remain elevated compared with uninfected populations [1]. Although ART dramatically improves the survival of infants [2] and children [1] and appears to improve the growth and neurologic function when initiated in older children [3, 4], less is known about the optimal time to initiate ART in older, asymptomatic children to prevent indolent HIV-associated morbidities, including loss of cognitive functions. The recommended CD4 cell count at which to start ART in adults and adolescents has been progressively revised upward [5]; however, this threshold remains controversial, and resulted in the split judgment by the 2011 Department of Health and Human Services panel on whether to recommend ART for all adults [5]. Current World Health Organization guidelines recommend the use of adult immunologic criteria (CD4 cell count, ,350 cells/lL) to determine when to initiate ART in children .5 years of age [6]. This leaves many relatively asymptomatic HIV-infected children with moderately decreased CD4 T-cell counts untreated, which could place them at risk for HIV-associated morbidity. (Normal CD4 cell counts in children 5–12 years of age range from 980 to 1200 cells/lL [7, 8]). In this issue of Clinical Infectious Diseases, Ruel et al [9] present a casecontrol study that demonstrates neurocognitive and motor dysfunction in ‘‘asymptomatic’’ HIV-infected children 6–12 years of age who do not qualify for ART. Their findings suggest that the World Health Organization guidelines do not capture early neurologic disease and provide a rationale to explore whether earlier ART would benefit these children. In children, progressive HIV encephalopathy (PHE) is a severe, potentially fatal, AIDS-defining illness that was common in the pre-ART era. It is defined as failure to achieve developmental milestones, or loss of previously acquired developmental milestones, impaired brain growth, and acquired symmetrical motor deficits (manifested by $2 of the following: paresis, pathologic reflexes, ataxia or gait disturbance) [10]. In the pre-ART era, the prevalence of PHE was 30%–50% [11]. With the use of ART, symptoms of those affected by PHE generally have improved, fatalities have become uncommon, and the incidence of PHE has dropped 10-fold [4, 11]. The study by Ruel et al carefully assessed neurocognitive and motor function in HIV-infected African children who did not qualify for ART and who were not considered encephalopathic by their referring physicians. The study used neurocognitive tests (Test of Variables of Attention [TOVA]; the Kaufman Assessment Battery for Children, 2nd edition [KABC-2]; and the Bruininks-Oseretsky Test of Motor Proficiency, 2nd edition [BOT-2]) to detect impairments in attention deficit and impulsivity, cognition, and motor function, respectively. The study does not provide an estimate of the prevalence of neurocognitive impairment but identifies subtle population-level differences between HIV-infected and uninfected children. This study is noteworthy because it suggests that, unlike PHE, which is rare in the era of ART, subtle neurocognitive and motor impairments affect a significant proportion of apparently asymptomatic HIV-infected children who do not yet qualify for ART. Unfortunately, the large-scale administration of the neurocognitive tests used by Ruel et al to prompt ART initiation is unrealistic in low resource settings owing to the time, space, and trained personnel needed for testing. Ideally, biomarkers and/or simple tests would identify early symptoms of neuropathology and serve as tools to monitor children who do not qualify for ART. Received 1 December 2011; accepted 9 December 2011. Correspondence: Lisa M. Frenkel, MD, Department of Pediatrics, Laboratory Medicine and Global Health, University of Washington, Children's Hospital and Research Institute, 1900 Ninth Avenue, Seattle, WA 98101-1304 (lfrenkel@uw.edu). Clinical Infectious Diseases The Author 2012. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@ oup.com. DOI: 10.1093/cid/cir1041

Novel insights in the fecal egg count reduction test for monitoring drug efficacy against soil-transmitted helminths in large-scale treatment programs.

BackgroundThe fecal egg count reduction test (FECRT) is recommended to monitor drug efficacy against soil-transmitted helminths (STHs) in public health. However, the impact of factors inherent to study design (sample size and detection limit of the fecal egg count (FEC) method) and host-parasite interactions (mean baseline FEC and aggregation of FEC across host population) on the reliability of FECRT is poorly understood.Methodology/Principal FindingsA simulation study was performed in which FECRT was assessed under varying conditions of the aforementioned factors. Classification trees were built to explore critical values for these factors required to obtain conclusive FECRT results. The outcome of this analysis was subsequently validated on five efficacy trials across Africa, Asia, and Latin America. Unsatisfactory (<85.0%) sensitivity and specificity results to detect reduced efficacy were found if sample sizes were small (<10) or if sample sizes were moderate (10–49) combined with highly aggregated FEC (k<0.25). FECRT remained inconclusive under any evaluated condition for drug efficacies ranging from 87.5% to 92.5% for a reduced-efficacy-threshold of 90% and from 92.5% to 97.5% for a threshold of 95%. The most discriminatory study design required 200 subjects independent of STH status (including subjects who are not excreting eggs). For this sample size, the detection limit of the FEC method and the level of aggregation of the FEC did not affect the interpretation of the FECRT. Only for a threshold of 90%, mean baseline FEC <150 eggs per gram of stool led to a reduced discriminatory power.Conclusions/SignificanceThis study confirms that the interpretation of FECRT is affected by a complex interplay of factors inherent to both study design and host-parasite interactions. The results also highlight that revision of the current World Health Organization guidelines to monitor drug efficacy is indicated. We, therefore, propose novel guidelines to support future monitoring programs.

Prevention of Mother-to-Child HIV-1 Transmission—Why We Still Need a Preventive HIV Immunization Strategy

There has been dramatic progress in identification of effective interventions to prevent mother-to-child HIV-1 transmission (PMTCT) in low-resource countries and rapid scaleup to implement these interventions in the last 5 years. The proportion of pregnant women tested for HIV-1 in low-resource countries has increased from 7% in 2005 to 26% in 2009, and the proportion of HIV-1–infected pregnant women receiving antiretroviral prophylaxis has increased from 15% in 2005 to 53% in 2009. A 24% reduction in estimated annual new infant HIV-1 infections was observed between 2005 and 2009 in the 25 low-resource countries, where approximately 91% of HIV-1–infected pregnant women reside. Joint United Nations Program on HIV/AIDS (UNAIDS) has developed a plan for global virtual elimination of mother-to-child HIV-1 transmission (MTCT), with a goal to reduce the number of new infant HIV-1 infections by 90% and MTCT to ,5% between 2009 and 2015. However, we remain far short of the goal of global MTCT elimination. In 2009, there remained an estimated 347,000 new infant infections in the 25 countries discussed above, with 40%–50% of these infections acquired through breastfeeding. Optimal prevention requires identification of maternal HIV-1 infection early in pregnancy with prompt initiation of antiretroviral drugs for treatment or prophylaxis, yet many women in lowresource countries access prenatal care late, only at delivery or do not deliver in medical settings. Provision of the infant PMTCT antiretroviral prophylaxis component remains low, with coverage increasing only slightly from 32% in 2008 to 35% in 2009. Although current World Health Organization guidelines now recommend breastfeeding for 12 months with concurrent infant or maternal antiretroviral prophylaxis, new reports suggest weaning before age 18 months is associated with elevated morbidity and mortality and that reduced risk of diarrhea-related morbidity and mortality among HIV-1–exposed uninfected children is associated with continuing breastfeeding after age 12 months even when replacement and complementary foods and counseling are provided. Thus, interventions to allow safe breastfeeding longer than 12 months are important to optimize infant survival. Finally, HIV-1 seroconversion rates of 3%–10% in uninfected pregnant or lactating women have been reported in HIV-1 endemic settings, which are associated with high risk of MTCT; it is estimated that 40% of new infant infections in Botswana are due to acute maternal infection during pregnancy or lactation. Although antiretroviral prophylaxis significantly reduces MTCT, effective implementation is complicated by need for prolonged drug administration and adherence, potential toxicities leading to continued monitoring requirements, potential for drug resistance, and inadequate health-care infrastructure. Additionally, even with maternal triple-drug prophylaxis, most studies demonstrate cumulative residual MTCT rates of 2%–5% at age 6 months. Thus, continued investigation of preventive immunologic interventions including maternal and/or infant passive/active immunization to reduce MTCT remains important. Although antiretroviral prophylaxis is the foundation for PMTCT, immunization strategies could provide a safe and durable adjunctive intervention to prevent transmission, particularly during breastfeeding. Immunization strategies, if found to be efficacious, have the advantage of being less reliant on patient adherence and health-care infrastructure than are drug interventions.

When to start ART in adults? The results of HPTN 052 move us closer to a test-and-treat policy

When is the best time to initiate antiretroviral therapy (ART) in adults? This is a vital question in HIV treatment and prevention services. More specifically, is the 350 cells/µl CD4 count threshold recommended by current World Health Organization (WHO) guidelines sufficient, or should we move to a ‘test-and-treat’ approach in which anyone who tests HIV-positive is offered ART, irrespective of their CD4 count? The recently announced results of the HPTN 052 trial take us closer, but not all the way, to a test-and-treat approach.

High transfusion failure rates in Malawian children with severe anaemia following a standard blood transfusion regimen

High transfusion failure rates in Malawian children with severe anaemia following a standard blood transfusion regimen

Antiretroviral therapy initiated soon after HIV diagnosis as standard care: potential to save lives?

In 2008, an estimated 33.4 million people were infected with human immunodeficiency virus (HIV) and ~4 million people were receiving antiretroviral therapy (ART). However, in 2007, an estimated 6.7 million people were in need of ART under the current World Health Organization guidelines, and 2.7 million more people became infected with HIV. Most of those not currently eligible for ART will become eligible within the next decade, making the current treatment strategy unsustainable. The development of cheaper, less toxic, and more potent antiretrovirals over the past decade has made it possible to consider novel strategies of arresting the HIV/AIDS epidemic. Evidence is growing that ART can be used to prevent HIV transmission and that earlier initiation of treatment is beneficial for those infected with HIV. A mathematical model predicts that by testing whole communities annually and treating all who are infected immediately, up to 7.2 million AIDS-related deaths could be prevented in the next 40 years, long-term funding required to fight the HIV epidemic could be reduced, and, most importantly, control of the HIV/ AIDS epidemic could be regained within 1–2 years of full-scale implementation of the strategy. We discuss the development of the concept of ART for the prevention of HIV transmission and the modeled impact that a test-and-treat strategy could have on the HIV epidemic, and consequently argue that a field trial should be carried out to confirm model parameters, highlight any practical problems, and test the model’s predictions.

Characteristics and Programme-Defined Treatment Outcomes among Childhood Tuberculosis (TB) Patients under the National TB Programme in Delhi

BackgroundChildhood tuberculosis (TB) patients under India's Revised National TB Control Programme (RNTCP) are managed using diagnostic algorithms and directly observed treatment with intermittent thrice-weekly short-course treatment regimens for 6–8 months. The assignment into pre-treatment weight bands leads to drug doses (milligram per kilogram) that are lower than current World Health Organization (WHO) guidelines for some patients.ObjectivesThe main aim of our study was to describe the baseline characteristics and treatment outcomes reported under RNTCP for registered childhood (age <15 years) TB patients in Delhi. Additionally, we compared the reported programmatic treatment completion rates between children treated as per WHO recommended anti-TB drug doses with those children treated with anti-TB drug doses below that recommended in WHO guidelines.MethodsFor this cross-sectional retrospective study, we reviewed programme records of all 1089 TB patients aged <15 years registered for TB treatment from January to June, 2008 in 6 randomly selected districts of Delhi. WHO disease classification and treatment outcome definitions are used by RNTCP, and these were extracted as reported in programme records.Results and ConclusionsAmong 1074 patients with records available, 651 (61%) were females, 122 (11%) were <5 years of age, 1000 (93%) were new cases, and 680 (63%) had extra-pulmonary TB (EP-TB)—most commonly peripheral lymph node disease [310 (46%)]. Among 394 pulmonary TB (PTB) cases, 165 (42%) were sputum smear-positive. The overall reported treatment completion rate was 95%. Similar reported treatment completion rates were found in all subgroups assessed, including those patients whose drug dosages were lower than that currently recommended by WHO. Further studies are needed to assess the reasons for the low proportion of under-5 years of age TB case notifications, address challenges in reaching all childhood TB patients by RNTCP, the accuracy of diagnosis, and the clinical validity of reported programme defined treatment completion.

Genital Ulcer Disease Treatment Policies and Access to Acyclovir in Eight Sub-Saharan African Countries

Herpes simplex virus-2, the most common cause of genital ulcer disease (GUD) globally, is a cofactor in human immunodeficiency virus type-1 (HIV-1) acquisition and transmission. Current World Health Organization guidelines for sexually transmitted infections recommend acyclovir as first-line syndromic treatment of GUD in countries with high herpes simplex virus-2 prevalence (> or =30%). To assess the extent of adoption of acyclovir as syndromic treatment for GUD, and describe procurement, distribution, and cost of acyclovir in the public and private sectors of 8 sub-Saharan African countries. We conducted standardized interviews with Ministry of Health (MoH) officials, pharmacists, and other pharmacy workers based in the public and private sectors. Interviews were conducted in Botswana, Kenya, Malawi, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe. Price comparisons were conducted using the 2007 median international reference price (IRP) for acyclovir. Of the 8 African countries, 4 surveyed had adopted acyclovir as first-line syndromic GUD treatment in both their essential medical lists and sexually transmitted infection guidelines. Country-specific acquisition prices for acyclovir 200 mg were comparable to the median IRP and ranged from 0.74 to 1.95 times the median IRP. The median retail cost of acyclovir in the private sector ranged from 5.85 to 9.76 times the median IRP. Public health facilities faced cost and regulatory barriers that impeded the requisitioning of acyclovir from the central medical stores. Systems for drug procurement, distribution, and access in sub-Saharan African countries need strengthening for a GUD treatment policy using acyclovir to be effective.

Application of a fluorescent dual stain to assess decontamination of tissue protein and prion amyloid from surgical stainless steel during simulated washer-disinfector cycles

Current World Health Organization guidelines pertaining to the reprocessing of surgical instruments in the face of potential iatrogenic transmission of Creutzfeldt-Jakob disease (iCJD) are incompatible for the vast majority of devices. This has led to the advent of a range of new decontamination measures. Even without the implementation of these new procedures, the incidence of proven iCJD through surgery remains low. In this study, existing decontamination processes in sterile service departments have been evaluated using simulated washer-disinfector cycles on surgical grade stainless steel wires inoculated with ME7 scrapie homogenate. The consequence of varying the soil drying times and choice of cycle pre-treatment on prion removal were evaluated. Assessment of residual contamination at each cycle phase was carried out with the application of a sensitive fluorescent staining procedure to identify both total protein and prion-associated amyloid. The study confirmed that immediate reprocessing following contamination was beneficial during the pre-treatment phase with either an enzymatic or pre-soak wetting agent. Final total protein levels at the end of the cycles, were not significantly different from those where the soil was allowed to dry. In addition, cycles involving a pre-treatment with either an enzymatic cleaner or pre-soak, whether the soil was allowed to dry or not, showed complete removal of detectable prion amyloid. The results suggest that current decontamination procedures, combined with immediate processing of surgical instruments, have the potential to be highly effective alone at reducing the risk of surgical transmission of CJD.

Cutaneous Presentation of Mantle Cell Lymphoma

© 2010 The Authors. doi: 10.2340/00015555-0886 Journal Compilation © 2010 Acta Dermato-Venereologica. ISSN 0001-5555 Mantle cell lymphoma (MCL) is a lymphoid malignancy of B-cells of the mantle zone or primary lymphoid follicle of lymph nodes. It is a moderately aggressive B-cell non-Hodgkin’s lymphoma (NHL). MCL represents only 6% of all NHL (1). MCL is listed in the new World Health Organization (WHO) European Organization for Research and Treatment for Cancer (EORTC) classification of cutaneous lymphomas that can secondarily involve the skin (2). According to this classification, “primary cutaneous lymphoma” refers to cutaneous T-cell lymphomas (CTCLs) and cutaneous B-cell lymphomas (CBCLs) that present in the skin with no evidence of extracutaneous disease at the time of diagnosis (2). The current WHO guidelines for the diagnosis of MCL rely on morphological examination and immunophenotyping with demonstration of cyclin D1 protein overexpression and/or the t(11;14)(q13;q32) translocation for confirmation (3). There are two primary B-cell lymphomas that are more common than MCL; cutaneous marginal zone Bcell lymphoma, and primary cutaneous follicle centre lymphoma. The former is an indolent cutaneous B-cell lymphoma derived from post-germinal centre cells and characterized by a proliferation of small lymphocytes, lymphoplasmo cytoid cells and plasma cells with monotypic cytoplasmic immunoglobulin. Follicle centre cell lymphoma is derived from follicle centre cells, consisting of a mixture of centrocytes and centroblasts (2, 4). Immunophenotyping assists in the differential diagnosis of these cutaneous lymphomas. Skin involvement in MCL is very rare (1). We describe here a case of MCL involving the skin as the first manifestation of the disease, and we review the clinical features of reported cases of MCL with skin lesions. CASE REpORT

Cost‐Effectiveness of Rotavirus Vaccination in Peru

There are plans to introduce the oral rotavirus vaccine Rotarix (GlaxoSmithKline), 1 of 2 recently developed vaccines against rotavirus, in Peru. We modeled the cost-effectiveness of adding a rotavirus vaccine to the Peruvian immunization program under 3 scenarios for the timing of vaccination: (1) strictly according to schedule, at 2 and 4 months of age (on time); (2) distributed around the target ages in the same way as the actual timings in the program (flexible); and (3) flexible but assuming vaccination is not initiated for infants >12 weeks of age (restricted). We assumed an introductory price of US $7.50 per dose, and varied the annual rate of price decrease in sensitivity analyses. The discounted cost per disability-adjusted life-year averted for restricted, flexible, and on-time schedules was $621, $615, and $581, respectively. For each of the 3 scenarios, the percentage reduction in deaths due to rotavirus infection was 53%, 66%, and 69%, respectively. The cost per disability-adjusted life-year averted for alternative "what-if" scenarios ranged from $229 (assuming a 1-dose schedule, administered on time) to $1491 (assuming a 2-dose schedule, with half the baseline vaccine efficacy rates and a restricted timing policy). On the basis of current World Health Organization guidelines, rotavirus vaccination represents a highly cost-effective intervention in Peru. Withholding the vaccine from children who present for their first dose after 12 weeks of age would reduce the number of deaths averted by approximately 20%. A single dose may be more cost-effective than 2 doses, but more evidence on the protection conferred by a single dose is required.