Ana-Claire Meyer

The impact of routine cryptococcal antigen screening on survival among HIV-infected individuals with advanced immunosuppression in Kenya

To test the hypothesis that a screening and treatment intervention for early cryptococcal infection would improve survival among HIV‐infected individuals with low CD4 cell counts.

Critical determinants of the epilepsy treatment gap: A cross-national analysis in resource-limited settings

Purpose:  Epilepsy is one of the most common serious neurologic disorders worldwide. Our objective was to determine which economic, health care, neurology, and epilepsy‐specific resources were associated with untreated epilepsy in resource‐constrained settings.

Is it time to rethink how neuropsychological tests are used to diagnose mild forms of HIV-associated neurocognitive disorders? Impact of false-positive rates on prevalence and power.

Background: Between 0 and 48% of normal HIV-uninfected individuals score below threshold neuropsychological test scores for HIV-associated neurocognitive disorders (HAND) or are false positives. There has been little effort to understand the effect of varied interpretations of research criteria for HAND on false-positive frequencies, prevalence and analytic estimates. Methods: The proportion of normal individuals scoring below Z score thresholds drawn from research criteria for HAND, or false-positive frequencies, was estimated in a normal Kenyan population and a simulated normal population using varied interpretations of research criteria for HAND. We calculated the impact of false-positive frequencies on prevalence estimates and statistical power. Results: False-positive frequencies of 2-74% were observed for asymptomatic neurocognitive impairment/mild neurocognitive disorder and 0-8% for HIV-associated dementia. False-positive frequencies depended on the definition of an abnormal cognitive domain, Z score thresholds and neuropsychological battery size. Misclassification led to clinically important overestimation of prevalence and dramatic decreases in power. Conclusions: Minimizing false-positive frequencies is critical to decrease bias in prevalence estimates and minimize reductions in power in studies of association, particularly for mild forms of HAND. We recommend changing the Z score threshold to ≤-1.5 for mild impairment, limiting analysis to 3-5 cognitive domains and using the average Z score to define an abnormal domain.

Utility of Quantitative Sensory Testing and Screening Tools in Identifying HIV-Associated Peripheral Neuropathy in Western Kenya: Pilot Testing

Background/Aim Neuropathy is the most common neurologic complication of HIV but is widely under-diagnosed in resource-constrained settings. We aimed to identify tools that accurately distinguish individuals with moderate/severe peripheral neuropathy and can be administered by non-physician healthcare workers (HCW) in resource-constrained settings. Methods We enrolled a convenience sample of 30 HIV-infected outpatients from a Kenyan HIV-care clinic. A HCW administered the Neuropathy Severity Score (NSS), Single Question Neuropathy Screen (Single-QNS), Subjective Peripheral Neuropathy Screen (Subjective-PNS), and Brief Peripheral Neuropathy Screen (Brief-PNS). Monofilament, graduated tuning fork, and two-point discrimination examinations were performed. Tools were validated against a neurologists clinical assessment of moderate/severe neuropathy. Results The sample was 57% male, mean age 38.6 years, and mean CD4 count 324 cells/µL. Neurologists assessment identified 20% (6/30) with moderate/severe neuropathy. Diagnostic utilities for moderate/severe neuropathy were: Single-QNS - 83% sensitivity, 71% specificity; Subjective-PNS-total - 83% sensitivity, 83% specificity; Subjective-PNS-max and NSS - 67% sensitivity, 92% specificity; Brief-PNS - 0% sensitivity, 92% specificity; monofilament - 100% sensitivity, 88% specificity; graduated tuning fork - 83% sensitivity, 88% specificity; two-point discrimination - 75% sensitivity, 58% specificity. Conclusions Pilot testing suggests Single-QNS, Subjective-PNS, and monofilament examination accurately identify HIV-infected patients with moderate/severe neuropathy and may be useful diagnostic tools in resource-constrained settings.

Lessons learned developing a diagnostic tool for HIV-associated dementia feasible to implement in resource-limited settings: Pilot testing in Kenya

Objective To conduct a preliminary evaluation of the utility and reliability of a diagnostic tool for HIV-associated dementia (HAD) for use by primary health care workers (HCW) which would be feasible to implement in resource-limited settings. Background In resource-limited settings, HAD is an indication for anti-retroviral therapy regardless of CD4 T-cell count. Anti-retroviral therapy, the treatment for HAD, is now increasingly available in resource-limited settings. Nonetheless, HAD remains under-diagnosed likely because of limited clinical expertise and availability of diagnostic tests. Thus, a simple diagnostic tool which is practical to implement in resource-limited settings is an urgent need. Methods A convenience sample of 30 HIV-infected outpatients was enrolled in Western Kenya. We assessed the sensitivity and specificity of a diagnostic tool for HAD as administered by a primary HCW. This was compared to an expert clinical assessment which included examination by a physician, neuropsychological testing, and in selected cases, brain imaging. Agreement between HCW and an expert examiner on certain tool components was measured using Kappa statistic. Results The sample was 57% male, mean age was 38.6 years, mean CD4 T-cell count was 323 cells/µL, and 54% had less than a secondary school education. Six (20%) of the subjects were diagnosed with HAD by expert clinical assessment. The diagnostic tool was 63% sensitive and 67% specific for HAD. Agreement between HCW and expert examiners was poor for many individual items of the diagnostic tool (K = .03–.65). This diagnostic tool had moderate sensitivity and specificity for HAD. However, reliability was poor, suggesting that substantial training and formal evaluations of training adequacy will be critical to enable HCW to reliably administer a brief diagnostic tool for HAD.

Nervous system disorders across the life course in resource-limited settings

The resiliency of the adult nervous system is markedly affected by the environment and the circumstances during infant and child development. As such, adults in resource-limited settings who may have experienced early deprivation are particularly vulnerable to subsequent neurological disorders. Adult populations in countries with relatively recent advances in economic development may still have a higher susceptibility to neurological illness or injury that is reflective of the socioeconomic environment that was present during that populations infancy and childhood. Brain and peripheral nervous system research conducted over the past decade in resource-limited settings has led to an impressive and growing body of knowledge that informs our understanding of neurological function and dysfunction, independent of geography. Neurological conditions feature prominently in the burgeoning epidemic of non-communicable diseases facing low- and middle-income countries. Neurological research in these countries is needed to address this burden of disease. Although the burden of more prevalent and severe neurological disease poses public health and clinical challenges in settings with limited neurological expertise, the same factors, along with genetic heterogeneity and the relative absence of ingrained clinical care practices, offer circumstances well-suited for the conduct of crucial future research that is globally relevant.This article has not been written or reviewed by Nature editors. Nature accepts no responsibility for the accuracy of the information provided.

Predictors of outcome in routine care for Cryptococcal meningitis in Western Kenya: lessons for HIV outpatient care in resource-limited settings

Purpose Cryptococcal meningitis is a leading cause of mortality among HIV-infected individuals in sub-Saharan Africa but little is known about its treatment and outcomes in decentralised HIV outpatient settings. We assessed adherence to treatment guidelines and determined predictors of survival. Design A computerised laboratory database identified HIV-infected adults with cryptococcal meningitis at Family AIDS Care and Education Services in Nyanza Province, Kenya, between 2005–2009. Medical records were reviewed. Kaplan-Meier survival curves were generated. Bivariate and multivariate Cox proportional hazards models were used to determine associations between key clinical characteristics and survival. Results Medical records were located for 79% (71/90). Mortality was 38% (27/71) over a median follow-up period of 201 days (IQR: 10–705 days). Adherence to local guidelines for treatment of cryptococcal meningitis was 48% (34/71). Higher body mass index was associated with improved survival (HR: 0.82, 95% CI (0.68 to 0.99)) even after controlling for factors such as age, CD4 cell count, receipt of highly active anti-retroviral therapy, and treatment with any anti-fungal therapy. Conclusions Cryptococcal meningitis diagnosed in routine HIV outpatient settings is largely treated as an outpatient and adherence to treatment guidelines is poor. Body mass index is a critical independent predictor of outcome. Additional research to determine the most effective strategies to reduce premature mortality is urgently needed.

Asymptomatic Cryptococcemia in Resource-Limited Settings

Despite increasing availability of anti-retroviral therapy, invasive cryptococcal disease continues to be a leading cause of death among HIV-infected individuals in resource-limited settings. Screening asymptomatic HIV-infected individuals with advanced immunosuppression for serum cryptococcal antigen clearly identifies a population at high risk of cryptococcal meningitis and death. However, screening with serum cryptococcal antigen alone identifies a heterogeneous clinical population, many of whom have mild clinical symptoms, sub-clinical meningeal infection, or fungemia. Currently, there is wide variation in practice and little evidence to guide the use of anti-fungal and anti-retroviral treatment for asymptomatic cryptococcal antigenemia (ACA). Furthermore, implementing a targeted screening and treatment intervention for ACA presents numerous operational challenges for already overburdened health care systems in resource-limited settings. While such an intervention shows promise, there are critical gaps in our understanding of ACA and its implications in the outpatient setting and an urgent need for additional research in this area.

Examining barriers to care: Provider and client perspectives on the stigmatization of HIV-positive Asian Americans with and without viral hepatitis co-infection

Abstract Between 1999 and 2003, Asian Americans and Pacific Islanders (APIs) in the US experienced more rapid growth in the number of AIDS cases than any other racial or ethnic group. In addition, the prevalence of HBV and HIV co-infection is estimated to be significantly higher among APIs in the US than in other racial/ethnic groups. High rates of HIV and hepatitis B or C (HBV and/or HCV) co-infection, in concert with language and cultural barriers, create significant challenges to effective coordination of treatment. The purpose of this study is to identify barriers to care and treatment in APIs with HIV with and without hepatitis co-infection. Specifically, we analyze results from semi-structured interviews with health care providers (N=23) and Asian Americans who are HIV and hepatitis (HBV and/or HCV) co-infected (N =17) in order to clarify how stigma in particular may impede/limit access to coordinated health care provision. Providers and clients recognize the need for integrated, culturally and linguistically appropriate access to care while simultaneously acknowledging that stigma is a severe barrier to access to care. This article sheds light on the complexities of the stigma experienced by HIV and hepatitis co-infected Asian Americans and suggests a need for further research and renewed efforts by caregivers to reduce stigma in these communities.

Training Needs and Evaluation of a Neuro-HIV Training Module for Non-Physician Healthcare Workers in Western Kenya

BACKGROUND Recent efforts to improve neurological care in resource-limited settings have focused on providing training to non-physician healthcare workers. METHODS A one-day neuro-HIV training module emphasizing HIV-associated dementia (HAD) and peripheral neuropathy was provided to 71 health care workers in western Kenya. Pre- and post-tests were administered to 55 participants. RESULTS Mean age of participants was 29 years, 53% were clinical officers and 40% were nurses. Self-reported comfort was significantly higher for treating medical versus neurologic conditions (p<0.001). After training, participants identified more neuropathy etiologies (pre=5.6/9 possible correct etiologies; post=8.0/9; p<0.001). Only 4% of participants at baseline and 6% (p=0.31) post-training could correctly identify HAD diagnostic criteria, though there were fewer mis-identified criteria such as abnormal level of consciousness (pre=82%; post=43%; p<0.001) and hallucinations (pre=57%; post=15%; p<0.001). CONCLUSIONS Healthcare workers were more comfortable treating medical than neurological conditions. This training significantly improved knowledge about etiologies of neuropathy and decreased some misconceptions about HAD.