Demographic and Clinical Features of Dengue Fever in Pakistan from 2003–2007: A Retrospective Cross-Sectional Study

Background

Demographic features of dengue fever have changed tremendously in Pakistan over the past two decades. Small scale studies from all over the country have reported different aspects of individual outbreaks during this time. However, there is scarcity of data looking at the overall trend of dengue virus infection in the country. In this study, we examined annual trends, seasonality, and clinical features of dengue fever in the Pakistani population.

Methods

Demographic information and dengue IgM status of all patients tested for dengue IgM antibody at Aga Khan University Hospital from January 2003 to December 2007 were analyzed to look for trends of IgM-positive cases in Pakistan. In addition, clinical and biochemical parameters were abstracted retrospectively from medical records of all patients hospitalized with IgM-proven dengue fever between January 2006 and December 2007. These patients were categorized into dengue fever and dengue hemorrhagic fever according to the WHO severity grading scale.

Results

Out of a total of 15040 patients (63.2% male and 36.8% female), 3952 (26.3%) tested positive for dengue IgM antibody. 209 IgM proven dengue patients were hospitalized during the study period. During 2003, IgM positive cases were seen only during the months of July-December. In contrast, such cases were detected throughout the year from the 2004–2007. The median age of IgM positive patients decreased every year from 32.0 years in 2003 to 24.0 years in 2007 (p<0.001). Among hospitalized patients, nausea was the most common presenting feature found in 124/209 (59.3%) patients. Children presented with a higher median body temperature than adults (p = 0.010). In addition, neutropenia was seen more commonly in children while raised serum ALT levels were seen more commonly in adults (both p = 0.006). While a low total white cell count was more common in patients with dengue fever as compared to Dengue Hemorrhagic Fever (p = 0.020), neutropenia (p = 0.019), monocytosis (p = 0.001) and raised serum ALT level (p = 0.005) were observed more commonly in the latter group.

Conclusions

Dengue virus is now endemic in Pakistan, circulating throughout the year with a peak incidence in the post monsoon period. Median age of dengue patients has decreased and younger patients may be more susceptible. Total and differential leukocyte counts may help identify patients at risk of hemorrhage.     

Migraine with Aura Is Associated with an Incomplete Circle of Willis: Results of a Prospective Observational Study

Objective

To compare the prevalence of an incomplete circle of Willis in patients with migraine with aura, migraine without aura, and control subjects, and correlate circle of Willis variations with alterations in cerebral perfusion.

Methods

Migraine with aura, migraine without aura, and control subjects were prospectively enrolled in a 1∶1∶1 ratio. Magnetic resonance angiography was performed to examine circle of Willis anatomy and arterial spin labeled perfusion magnetic resonance imaging to measure cerebral blood flow. A standardized template rating system was used to categorize circle of Willis variants. The primary pre-specified outcome measure was the frequency of an incomplete circle of Willis. The association between circle of Willis variations and cerebral blood flow was also analyzed.

Results

170 subjects were enrolled (56 migraine with aura, 61 migraine without aura, 53 controls). An incomplete circle of Willis was significantly more common in the migraine with aura compared to control group (73% vs. 51%, p = 0.02), with a similar trend for the migraine without aura group (67% vs. 51%, p = 0.08). Using a quantitative score of the burden of circle of Willis variants, migraine with aura subjects had a higher burden of variants than controls (p = 0.02). Compared to those with a complete circle, subjects with an incomplete circle had greater asymmetry in hemispheric cerebral blood flow (p = 0.05). Specific posterior cerebral artery variants were associated with greater asymmetries of blood flow in the posterior cerebral artery territory.

Conclusions

An incomplete circle of Willis is more common in migraine with aura subjects than controls, and is associated with alterations in cerebral blood flow.     

Clinical Utility of a Commercial LAM-ELISA Assay for TB Diagnosis in HIV-Infected Patients Using Urine and Sputum Samples

Background

The accurate diagnosis of TB in HIV-infected patients, particularly with advanced immunosuppression, is difficult. Recent studies indicate that a lipoarabinomannan (LAM) assay (Clearview-TB®-ELISA) may have some utility for the diagnosis of TB in HIV-infected patients; however, the precise subgroup that may benefit from this technology requires clarification. The utility of LAM in sputum samples has, hitherto, not been evaluated.

Methods

LAM was measured in sputum and urine samples obtained from 500 consecutively recruited ambulant patients, with suspected TB, from 2 primary care clinics in South Africa. Culture positivity for M. tuberculosis was used as the reference standard for TB diagnosis.

Results

Of 440 evaluable patients 120/387 (31%) were HIV-infected. Urine-LAM positivity was associated with HIV positivity (p = 0.007) and test sensitivity, although low, was significantly higher in HIV-infected compared to uninfected patients (21% versus 6%; p<0.001), and also in HIV-infected participants with a CD4 <200 versus >200 cells/mm³ (37% versus 0%; p = 0.003). Urine-LAM remained highly specific in all 3 subgroups (95%–100%). 25% of smear-negative but culture-positive HIV-infected patients with a CD4 <200 cells/mm³ were positive for urine-LAM. Sputum-LAM had good sensitivity (86%) but poor specificity (15%) likely due to test cross-reactivity with several mouth-residing organisms including actinomycetes and nocardia species.

Conclusions

These preliminary data indicate that in a high burden primary care setting the diagnostic usefulness of urine-LAM is limited, as a rule-in test, to a specific patient subgroup i.e. smear-negative HIV-infected TB patients with a CD4 count <200 cells/mm³, who would otherwise have required further investigation. However, even in this group sensitivity was modest. Future and adequately powered studies in a primary care setting should now specifically target patients with suspected TB who have advanced HIV infection.     

Development and Validation of a Bedside Score to Predict Early Death in Cancer of Unknown Primary Patients

Background

We have investigated predictors of 90-day-mortality in a large cohort of non-specific cancer of unknown primary patients.

Methods

Predictors have been identified by univariate and then logistic regression analysis in a single-center cohort comprising 429 patients (development cohort). We identified four predictors that produced a predictive score that has been applied to an independent multi-institutional cohort of 409 patients (validation cohort). The score was the sum of predictors for each patient (0 to 4).

Results

The 90-day-mortality-rate was 33 and 26% in both cohorts. Multivariate analysis has identified 4 predictors for 90-day-mortality: performance status>1 (OR = 3.03, p = 0.001), at least one co-morbidity requiring treatment (OR = 2.68, p = 0.004), LDH>1.5×the upper limit of normal (OR = 2.88, p = 0.007) and low albumin or protein levels (OR = 3.05, p = 0.007). In the development cohort, 90-day-mortality-rates were 12.5%, 32% and 64% when the score was [0–1], 2 and [3]–[4], respectively. In the validation cohort, risks were 13%, 25% and 62% according to the same score values.

Conclusions

We have validated a score that is easily calculated at the beside that estimates the 90-days mortality rate in non-specific CUP patients. This could be helpful to identify patients who would be better served with palliative care rather than aggressive chemotherapy.     

Malaria Prevention with IPTp during Pregnancy Reduces Neonatal Mortality

Background

In the global context of a reduction of under-five mortality, neonatal mortality is an increasingly relevant component of this mortality. Malaria in pregnancy may affect neonatal survival, though no strong evidence exists to support this association.

Methods

In the context of a randomised, placebo-controlled trial of intermittent preventive treatment (IPTp) with sulphadoxine-pyrimethamine (SP) in 1030 Mozambican pregnant women, 997 newborns were followed up until 12 months of age. There were 500 live borns to women who received placebo and 497 to those who received SP.

Findings

There were 58 infant deaths; 60.4% occurred in children born to women who received placebo and 39.6% to women who received IPTp (p = 0.136). There were 25 neonatal deaths; 72% occurred in the placebo group and 28% in the IPTp group (p = 0.041). Of the 20 deaths that occurred in the first week of life, 75% were babies born to women in the placebo group and 25% to those in the IPTp group (p = 0.039). IPTp reduced neonatal mortality by 61.3% (95% CI 7.4%, 83.8%); p = 0.024].

Conclusions

Malaria prevention with SP in pregnancy can reduce neonatal mortality. Mechanisms associated with increased malaria infection at the end of pregnancy may explain the excess mortality in the malaria less protected group. Alternatively, SP may have reduced the risk of neonatal infections. These findings are of relevance to promote the implementation of IPTp with SP, and provide insights into the understanding of the pathophysiological mechanisms through which maternal malaria affects fetal and neonatal health.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00209781","term_id":"NCT00209781"}}NCT00209781     

Low Acceptability of A/H1N1 Pandemic Vaccination in French Adult Population: Did Public Health Policy Fuel Public Dissonance?

Background

In July 2009, French public health authorities embarked in a mass vaccination campaign against A/H1N1 2009 pandemic-influenza. We explored the attitudes and behaviors of the general population toward pandemic vaccination.

Methodology/Principal Findings

We conducted a cross-sectional online survey among 2,253 French representative adults aged 18 to 64 from November 17 to 25, 2009 (completion rate: 93.8%). The main outcome was the acceptability of A/H1N1 vaccination as defined by previous receipt or intention to get vaccinated (“Yes, certainly”, “Yes, probably”). Overall 17.0% (CI 95%, 15.5% to 18.7%) of respondents accepted A/H1N1 vaccination. Independent factors associated with acceptability included: male sex (p = .0001); older age (p = .002); highest or lowest level of education (p = .016); non-clerical occupation (p = .011); having only one child (p = .008); and having received seasonal flu vaccination in prior 3 years (p<.0001). Acceptability was also significantly higher among pregnant women (37.9%) and other at risk groups with chronic diseases (34.8%) (p = .002). Only 35.5% of respondents perceived A/H1N1 influenza illness as a severe disease and 12.7% had experienced A/H1N1 cases in their close relationships with higher acceptability (p<.0001 and p = .006, respectively). In comparison to 26.0% respondents who did not consult their primary care physician, acceptability was significantly higher among 8.0% respondents who were formally advised to get vaccinated, and lower among 63.7% respondents who were not advised to get vaccinated (respectively: 15.8%, 59.5% and 11.7%- p<.0001). Among respondents who refused vaccination, 71.2% expressed concerns about vaccine safety.

Conclusions/Significance

Our survey occurred one week before the peak of the pandemic in France. We found that alarming public health messages aiming at increasing the perception of risk severity were counteracted by daily personal experience which did not confirm the threat, while vaccine safety was a major issue. This dissonance may have been amplified by having not involved primary care physicians in the mass vaccination campaign.     

Alcoholism and Strongyloides stercoralis: Daily Ethanol Ingestion Has a Positive Correlation with the Frequency of Strongyloides Larvae in the Stools

Background

Significantly higher prevalence of Strongyloides stercoralis has been reported in chronic alcoholic patients. The aim of this investigation was to report the prevalence of Strongyloides larvae in stools of chronic alcoholic patients with known daily ethanol intake.

Methods

From January 2001 through December 2003 the results of fecal examinations and the daily ethanol intake were retrieved from the records of 263 chronic alcoholic and from 590 non-alcoholic male patients that sought health care at the outpatients unit of the University Hospital C A Moraes. Alcoholic patients were separated into four groups, with 150g intervals between the groups according to the daily ethanol intake.

Results

(a) The frequency of Strongyloides was significantly higher in alcoholic patients than in control group (overall prevalence in alcoholic 20.5% versus 4.4% in control group; p = 0.001). Even in the group with a daily intake of ethanol equal to or less than 150g the prevalence was higher than in control group, although non significant (9.5%, versus 4.4% in control group; p = 0,071); (b) the prevalence of Strongyloides in alcoholic patients rises with the increase of ethanol intake (Pearson''s Correlation Coefficient = 0.956; p = 0.022), even in patients without liver cirrhosis (Pearson''s Correlation Coefficient = 0.927; p = 0.037).

Conclusion

These results confirm and reinforce the hypothesis that chronic alcoholism is associated with Strongyloides infection, which is in direct relationship with the severity of alcoholism, independently of the presence of liver cirrhosis.     

Sensitivity of Five Rapid HIV Tests on Oral Fluid or Finger-Stick Whole Blood: A Real-Time Comparison in a Healthcare Setting

Background

Health authorities in several countries recently recommended the expansion of human immunodeficiency virus (HIV) antibody testing, including the use of rapid tests. Several HIV rapid tests are now licensed in Europe but their sensitivity on total blood and/or oral fluid in routine healthcare settings is not known.

Methods and Findings

200 adults with documented HIV-1 (n = 194) or HIV-2 infection (n = 6) were prospectively screened with five HIV rapid tests using either oral fluid (OF) or finger-stick whole blood (FSB). The OraQuick Advance rapid HIV1/2® was first applied to OF and then to FSB, while the other tests were applied to FSB, in the following order: Vikia HIV 1/2®, Determine HIV 1–2®, Determine® HIV-1/2 Ag/Ab Combo® and INSTI HIV-1/HIV-2®. Tests negative on FSB were repeated on paired serum samples. Twenty randomly selected HIV-seronegative subjects served as controls, and the results were read blindly. Most patients had HIV-1 subtype B infection (63.3%) and most were on antiretroviral therapy (68.5%). Sensitivity was 86.5%, 94.5%, 98.5%, 94.9%, 95.8% and 99% respectively, with OraQuick OF, OraQuick FSB, Vikia, Determine, Determine Ag/Ab Combo and INSTI (p<0.0001). OraQuick was less sensitive on OF than on FSB (p = 0.008). Among the six patients with three or more negative tests, two had recent HIV infection and four patients on antiretroviral therapy had undetectable plasma viral load. When patients positive in all the tests were compared with patients who had at least one negative test, only a plasma HIV RNA level <200 cp/ml was significantly associated with a false-negative result (p = 0.009). When the 33 rapid tests negative on FSB were repeated on serum, all but six (5 negative with OraQuick, 1 with INSTI) were positive. The sensitivity of OraQuick, Determine and Determine Ag/Ab Combo was significantly better on serum than on FSB (97.5%, p = 0.04; 100%, p = 0.004; and 100%, p = 0.02, respectively).

Conclusion

When evaluated in a healthcare setting, rapid HIV tests were less sensitive on oral fluid than on finger-stick whole blood and less sensitive on finger-stick whole blood than on serum.     

Early In-Hospital Mortality following Trainee Doctors' First Day at Work

Background

There is a commonly held assumption that early August is an unsafe period to be admitted to hospital in England, as newly qualified doctors start work in NHS hospitals on the first Wednesday of August. We investigate whether in-hospital mortality is higher in the week following the first Wednesday in August than in the previous week.

Methodology

A retrospective study in England using administrative hospital admissions data. Two retrospective cohorts of all emergency patients admitted on the last Wednesday in July and the first Wednesday in August for 2000 to 2008, each followed up for one week.

Principal Findings

The odds of death for patients admitted on the first Wednesday in August was 6% higher (OR 1.06, 95% CI 1.00 to 1.15, p = 0.05) after controlling for year, gender, age, socio-economic deprivation and co-morbidity. When subdivided into medical, surgical and neoplasm admissions, medical admissions admitted on the first Wednesday in August had an 8% (OR 1.08, 95% CI 1.01 to 1.16, p = 0.03) higher odds of death. In 2007 and 2008, when the system for junior doctors'' job applications changed, patients admitted on Wednesday August 1^st had 8% higher adjusted odds of death than those admitted the previous Wednesday, but this was not statistically significant (OR 1.08, 95% CI 0.95 to 1.23, p = 0.24).

Conclusions

We found evidence that patients admitted on the first Wednesday in August have a higher early death rate in English hospitals compared with patients admitted on the previous Wednesday. This was higher for patients admitted with a medical primary diagnosis.     

Natural Killer Cells in Obesity: Impaired Function and Increased Susceptibility to the Effects of Cigarette Smoke

Background

Obese individuals who smoke have a 14 year reduction in life expectancy. Both obesity and smoking are independantly associated with increased risk of malignancy. Natural killer cells (NK) are critical mediators of anti-tumour immunity and are compromised in obese patients and smokers. We examined whether NK cell function was differentially affected by cigarette smoke in obese and lean subjects.

Methodology and Principal Findings

Clinical data and blood were collected from 40 severely obese subjects (BMI>40 kg/m²) and 20 lean healthy subjects. NK cell levels and function were assessed using flow cytometry and cytotoxicity assays. The effect of cigarette smoke on NK cell ability to kill K562 tumour cells was assessed in the presence or absence of the adipokines leptin and adiponectin. NK cell levels were significantly decreased in obese subjects compared to lean controls (7.6 vs 16.6%, p = 0.0008). NK function was also significantly compromised in obese patients (30% +/− 13% vs 42% +/−12%, p = 0.04). Cigarette smoke inhibited NK cell ability to kill tumour cell lines (p<0.0001). NK cells from obese subjects were even more susceptible to the inhibitory effects of smoke compared to lean subjects (33% vs 28%, p = 0.01). Cigarette smoke prevented NK cell activation, as well as perforin and interferon-gamma secretion upon tumour challenge. Adiponectin but not leptin partially reversed the effects of smoke on NK cell function in both obese (p = 0.002) and lean controls (p = 0.01).

Conclusions/Significance

Obese subjects have impaired NK cell activity that is more susceptible to the detrimental effects of cigarette smoke compared to lean subjects. This may play a role in the increase of cancer and infection seen in this population. Adiponectin is capable of restoring NK cell activity and may have therapeutic potential for immunity in obese subjects and smokers.     

The Impact of HIV Infection and CD4 Cell Count on the Performance of an Interferon Gamma Release Assay in Patients with Pulmonary Tuberculosis

Background

The performance of the tuberculosis specific Interferon Gamma Release Assays (IGRAs) has not been sufficiently documented in tuberculosis- and HIV-endemic settings. This study evaluated the sensitivity of the QuantiFERON TB-Gold In-Tube (QFT-IT) in patients with culture confirmed pulmonary tuberculosis (PTB) in a TB- and HIV-endemic population and the effect of HIV-infection and CD4 cell count on test performance.

Methodology/Principal Findings

161 patients with sputum culture confirmed PTB were subjected to HIV- and QFT-IT testing and measurement of CD4 cell count. The QFT-IT was positive in 74% (119/161; 95% CI: 67–81%). Sensitivity was higher in HIV-negative (75/93) than in HIV-positive (44/68) patients (81% vs. 65%, p = 0.02) and increased with CD4 cell count in HIV-positive patients (test for trend p = 0.03). 23 patients (14%) had an indeterminate result and this proportion decreased with increasing CD4 cell count in HIV-positive patients (test for trend p = 0.03). Low CD4 cell count (<300 cells/µl) did not account for all QFT-IT indeterminate nor all negative results. Sensitivity when excluding indeterminate results was 86% (95% CI: 81–92%) and did not differ between HIV-negative and HIV–positive patients (88 vs. 83%, p = 0.39).

Conclusions/Significance

Sensitivity of the QFT-IT for diagnosing active PTB infection was reasonable when excluding indeterminate results and in HIV-negative patients. However, since the test missed more than 10% of patients, its potential as a rule-out test for active TB disease is limited. Furthermore, test performance is impaired by low CD4 cell count in HIV-positive patients and possibly by other factors as well in both HIV-positive and HIV-negative patients. This might limit the potential of the test in populations where HIV-infection is prevalent.     

Will Patients Benefit from Regionalization of Gynecologic Cancer Care?

Objective

Patient chances for cure and palliation for a variety of malignancies may be greatly affected by the care provided by a treating hospital. We sought to determine the effect of volume and teaching status on patient outcomes for five gynecologic malignancies: endometrial, cervical, ovarian and vulvar carcinoma and uterine sarcoma.

Methods

The Florida Cancer Data System dataset was queried for all patients undergoing treatment for gynecologic cancers from 1990–2000.

Results

Overall, 48,981 patients with gynecologic malignancies were identified. Endometrial tumors were the most common, representing 43.2% of the entire cohort, followed by ovarian cancer (30.9%), cervical cancer (20.8%), vulvar cancer (4.6%), and uterine sarcoma (0.5%). By univariate analysis, although patients treated at high volume centers (HVC) were significantly younger, they benefited from an improved short-term (30-day and/or 90-day) survival for cervical, ovarian and endometrial cancers. Multivariate analysis (MVA), however, failed to demonstrate significant survival benefit for gynecologic cancer patients treated at teaching facilities (TF) or HVC. Significant prognostic factors at presentation by MVA were age over 65 (HR = 2.6, p<0.01), African-American race (HR = 1.36, p<0.01), and advanced stage (regional HR = 2.08, p<0.01; advanced HR = 3.82, p<0.01, respectively). Surgery and use of chemotherapy were each significantly associated with improved survival.

Conclusion

No difference in patient survival was observed for any gynecologic malignancy based upon treating hospital teaching or volume status. Although instances of improved outcomes may occur, overall further regionalization would not appear to significantly improve patient survival.     

Application of ICHD-II Criteria in a Headache Clinic of China

Background

China has the huge map and the largest population in the world. Previous studies on the prevalence and classification of headaches were conducted based on the general population, however, similar studies among the Chinese outpatient population are scarce. This study aimed to analyze the characteristics of 1843 headache patients enrolled in a North China headache clinic of the General Hospital for Chinese People''s Liberation Army from October 2011 to May 2012, with the International Classification of Headache Disorders, 2nd Edition (ICHD-II).

Methods and Results

Personal interviews were carried out and a detailed questionnaire was used to collect medical records including age, sex and headache characteristics. Patients came from 28 regions of China with the median age of 40.9 (9–80) years and the female/male ratio of 1.67/1. The primary headaches (78.4%) were classified as the following: migraine (39.1%), tension-type headache (32.5%), trigeminal autonomic cephalalgias (5.3%) and other primary headache (1.5%). Among the rest patients, 12.9% were secondary headaches, 5.9% were cranial neuralgias and 2.5% were unspecified or not elsewhere classified. Fourteen point nine percent (275/1843) were given an additional diagnosis of chronic daily headache, including medication-overuse headache (MOH, 49.5%), chronic tension-type headache (CTTH, 32.7%) and chronic migraine (CM, 13.5%). The visual analogue scale (VAS) score of TTH with MOH was significantly higher than that of CTTH (6.8±2.0 vs 5.6±2.0, P<0.001). The similar result was also observed in VAS score between migraine with MOH and CM (8.0±1.5 vs 7.0±1.5, P = 0.004). The peak age at onset of TTH for male and female were both in the 3^rd decade of life. However, the age distribution at onset of migraine shows an obvious sex difference, i.e. the 2^nd decade for females and the 1^st decade for males.

Conclusions/Significance

This study revealed the characteristics of the headache clinic outpatients in a tertiary hospital of North China that migraine is the most common diagnosis. Furthermore, most headaches in this patient population can be classified using ICHD-II criteria.     

Impact of HIV Infection and Kaposi Sarcoma on Human Herpesvirus-8 Mucosal Replication and Dissemination in Uganda

Introduction

Kaposi sarcoma (KS) is the leading cause of cancer in Uganda and occurs in people with and without HIV. Human herpesvirus-8 (HHV-8) replication is important both in transmission of HHV-8 and progression to KS. We characterized the sites and frequency of HHV-8 detection in Ugandans with and without HIV and KS.

Methods

Participants were enrolled into one of four groups on the basis of HIV and KS status (HIV negative/KS negative, HIV positive/KS negative, HIV negative/KS positive, and HIV positive/KS positive). Participants collected oral swabs daily and clinicians collected oral swabs, anogenital swabs, and plasma samples weekly over 4 weeks. HHV-8 DNA at each site was quantified by polymerase chain reaction (PCR).

Results

78 participants collected a total of 2063 orals swabs and 358 plasma samples. Of these, 428 (21%) oral swabs and 96 (27%) plasma samples had detectable HHV-8 DNA. HHV-8 was detected more frequently in both the oropharynx of persons with KS (24 (57%) of 42 persons with KS vs. 8 (22%) of 36 persons without, p = 0.002) and the peripheral blood (30 (71%) of 42 persons with KS vs. 8 (22%) of 36 persons without, p<0.001). In a multivariate model, HHV-8 viremia was more frequent among men (IRR = 3.3, 95% CI = 1.7–6.2, p<0.001), persons with KS (IRR = 3.9, 95% CI = 1.7–9.0, p = 0.001) and persons with HIV infection (IRR = 1.7, 95% CI = 1.0–2.7, p = 0.03). Importantly, oral HHV-8 detection predicted the subsequent HHV-8 viremia. HHV-8 viremia was significantly more common when HHV-8 DNA was detected from the oropharynx during the week prior than when oral HHV-8 was not detected (RR = 3.3, 95% CI = 1.8–5.9 p<0.001). Genital HHV-8 detection was rare (9 (3%) of 272 swabs).

Conclusions

HHV-8 detection is frequent in the oropharynx and peripheral blood of Ugandans with endemic and epidemic KS. Replication at these sites is highly correlated, and viremia is increased in men and those with HIV. The high incidence of HHV-8 replication at multiple anatomic sites may be an important factor leading to and sustaining the high prevalence of KS in Uganda.     

Meta-Analysis of the Relationship between Multiple Sclerosis and Migraine

Background

Studies investigating a proposed association between multiple sclerosis (MS) and migraine have produced conflicting results and a great range in the prevalence rate of migraine in MS patients. By meta-analysing all available data we aimed to establish an overall estimate of any association in order to more accurately inform clinicians and care-givers about a potential association between MS and migraine.

Methods

Pubmed and EMBASE were searched to identify suitable studies. Studies were included if they were a case-control study or cohort study in which controls were not reported to have another neurological condition, were available in English, and specified migraine as a headache sub-type. The odds ratio (OR) of migraine in MS patients vs. controls was calculated using the inverse variance with random effects model in Review Manager 5.1.

Results

Eight studies were selected for inclusion, yielding a total of 1864 MS patients and 261563 control subjects. We found a significant association between migraine and MS (OR = 2.60, 95% CI 1.12–6.04), although there was significant heterogeneity. Sensitivity analysis showed that migraine without aura was associated with MS OR = 2.29 (95% CI 1.14–4.58), with no significant heterogeneity.

Conclusions

MS patients are more than twice as likely to report migraine as controls. Care providers should be alerted to ask MS patients about migraine in order to treat it and potentially improve quality of life. Future work should further investigate the temporal relationship of this association and relationship to the clinical characteristics of MS.     

Taenia solium Cysticercosis Hotspots Surrounding Tapeworm Carriers: Clustering on Human Seroprevalence but Not on Seizures

Background

Neurocysticercosis accounts for 30%–50% of all late-onset epilepsy in endemic countries. We assessed the clustering patterns of Taenia solium human cysticercosis seropositivity and seizures around tapeworm carriers in seven rural communities in Peru.

Methodology

The presence of T. solium–specific antibodies was defined as one or more positive bands in the enzyme-linked immunoelectrotransfer blot (EITB). Neurocysticercosis-related seizures cases were diagnosed clinically and had positive neuroimaging or EITB.

Principal Findings

Eleven tapeworm carriers were identified by stool microscopy. The seroprevalence of human cysticercosis was 24% (196/803). Seroprevalence was 21% >50 m from a carrier and increased to 32% at 1–50 m (p = 0.047), and from that distance seroprevalence had another significant increase to 64% at the homes of carriers (p = 0.004). Seizure prevalence was 3.0% (25/837) but there were no differences between any pair of distance ranges (p = 0.629, Wald test 2 degrees of freedom).

Conclusion/Significance

We observed a significant human cysticercosis seroprevalence gradient surrounding current tapeworm carriers, although cysticercosis-related seizures did not cluster around carriers. Due to differences in the timing of the two outcomes, seroprevalence may reflect recent T. solium exposure more accurately than seizure frequency.     

C-Reactive Protein,Erythrocyte Sedimentation Rate and Orthopedic Implant Infection

Background

C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) have been shown to be useful for diagnosis of prosthetic hip and knee infection. Little information is available on CRP and ESR in patients undergoing revision or resection of shoulder arthroplasties or spine implants.

Methods/Results

We analyzed preoperative CRP and ESR in 636 subjects who underwent knee (n = 297), hip (n = 221) or shoulder (n = 64) arthroplasty, or spine implant (n = 54) removal. A standardized definition of orthopedic implant-associated infection was applied. Receiver operating curve analysis was used to determine ideal cutoff values for differentiating infected from non-infected cases. ESR was significantly different in subjects with aseptic failure infection of knee (median 11 and 53.5 mm/h, respectively, p = <0.0001) and hip (median 11 and 30 mm/h, respectively, p = <0.0001) arthroplasties and spine implants (median 10 and 48.5 mm/h, respectively, p = 0.0033), but not shoulder arthroplasties (median 10 and 9 mm/h, respectively, p = 0.9883). Optimized ESR cutoffs for knee, hip and shoulder arthroplasties and spine implants were 19, 13, 26, and 45 mm/h, respectively. Using these cutoffs, sensitivity and specificity to detect infection were 89 and 74% for knee, 82 and 60% for hip, and 32 and 93% for shoulder arthroplasties, and 57 and 90% for spine implants. CRP was significantly different in subjects with aseptic failure and infection of knee (median 4 and 51 mg/l, respectively, p<0.0001), hip (median 3 and 18 mg/l, respectively, p<0.0001), and shoulder (median 3 and 10 mg/l, respectively, p = 0.01) arthroplasties, and spine implants (median 3 and 20 mg/l, respectively, p = 0.0011). Optimized CRP cutoffs for knee, hip, and shoulder arthroplasties, and spine implants were 14.5, 10.3, 7, and 4.6 mg/l, respectively. Using these cutoffs, sensitivity and specificity to detect infection were 79 and 88% for knee, 74 and 79% for hip, and 63 and 73% for shoulder arthroplasties, and 79 and 68% for spine implants.

Conclusion

CRP and ESR have poor sensitivity for the diagnosis of shoulder implant infection. A CRP of 4.6 mg/l had a sensitivity of 79 and a specificity of 68% to detect infection of spine implants.     

Adverse Events in a Cohort of HIV Infected Pregnant and Non-Pregnant Women Treated with Nevirapine versus Non-Nevirapine Antiretroviral Medication

Background

Predictors of adverse events (AE) associated with nevirapine use are needed to better understand reports of severe rash or liver enzyme elevation (LEE) in HIV+ women.

Methodology

AE rates following ART initiation were retrospectively assessed in a multi-site cohort of 612 women. Predictors of onset of rash or LEE were determined using univariate and multivariate analyses.

Principal Findings

Of 612 subjects, 152 (24.8%) initiated NVP-based regimens with 86 (56.6%) pregnant; 460 (75.2%) initiated non-NVP regimens with 67 (14.6%) pregnant.

LEE

No significant difference was found between regimens in the development of new grade ≥2 LEE (p = 0.885). Multivariate logistic regression demonstrated an increased likelihood of LEE with HCV co-infection (OR 2.502, 95% CI: 1.04 to 6, p = 0.040); pregnancy, NVP-based regimen, and baseline CD4 >250 cells/mm³ were not associated with this toxicity.

Rash

NVP initiation was associated with rash after controlling for CD4 and pregnancy (OR 2.78; 95%CI: 1.14–6.76), as was baseline CD4 >250 cells/mm³ when controlling for pregnancy and type of regimen (OR 2.68; 95% CI: 1.19–6.02 p = 0.017).

Conclusions

CD4 at initiation of therapy was a predictor of rash but not LEE with NVP use in HIV+ women. Pregnancy was not an independent risk factor for the development of AEs assessed. The findings from this study have significant implications for women of child-bearing age initiating NVP-based ART particularly in resource limited settings. This study sheds more confidence on the lack of LEE risk and the need to monitor rash with the use of this medication.