Sensitivity and specificity of cryptococcal antigen lateral flow assay for the diagnosis of HIV-associated cryptococcal meningitis in western Kenya

Background: HIV-associated cryptococcal meningitis carries a high case-fatality-rate in sub-Saharan Africa. Diagnostic delays partly contribute to this. Rapid point-of-care tests may facilitate speedy diagnosis. This study aimed to determine the sensitivity and specificity of urine, serum and cerebrospinal fluid (CSF) cryptococcal antigen lateral flow assay for the diagnosis of HIV-associated cryptococcal meningitis compared with the gold standard CSF culture.Methods: A cross-sectional study was conducted in the medical wards of Moi Teaching and Referral Hospital, Eldoret, Kenya. Adult (≥18years) HIV-infected in-patients suspected to have meningitis had paired samples of urine, serum and CSF collected and tested real time using the cryptococcal antigen lateral flow assay (rapid point of care test). CSF cultures were also conducted. Data were analyzed using STATA ® (Statacorp Texas USA®). Descriptive statistics were used to summarize demographic, clinical and laboratory parameters. Sensitivity and specificity of the rapid test were calculated with the CSF culture as the gold standard.Results: Of the 302 participants included 172 (57%) were female, median age 37 years (IQR 30-45). The median CD4+ cell count was 183/ul (IQR 54-333). Among 288 participants with available CSF culture results, 50(17%) had culture-confirmed cryptococcal meningitis. Urine rapid test had a sensitivity and specificity of 86 %( 95% CI 73-94) and 95.7% (95% CI 92-98) respectively. Serum rapid test had a sensitivity and specificity of 92% (95%CI 81-98) and 94.9% (95%CI 91-97) respectively. CSF rapid test had a sensitivity and specificity of 92% (95%CI 81-98%) and 94.5% (95% CI 91-97) respectively. Conclusion: Serum and CSF cryptococcal antigen lateral flow assay are highly sensitive and specific for the diagnosis of HIV-associated cryptococcal meningitis. Urine is relatively sensitive and specific. Serum and CSF cryptococcal antigen lateral flow assay can be used as a less expensive alternative to cryptococcal antigen latex agglutination method. Urine cryptococcal antigen lateral flow assay could be adopted as a rapid point of care diagnostic test in primary care clinics in low income settings without experience in handling CSF or serum, to fast track diagnosis of cryptococcal meningitis

Research Brief 10-02-HNP

Despite the knowledge and information available about HIV, stigma is still present. The affects of stigma are real and tangible. Globally HIV positive people are marginalized and often dread that their HIV status will adversely affect them socially. The belief that HIV-infected people are somehow deviant, or misconceptions about the mode of transmission fuels anxiety, fear, and distrust, which translates into barriers to adequate health care, emotional distress, and actions that can have adverse affects on health outcomes. When working with HIV-infected individuals and those at risk of becoming infected with HIV, the impact of stigma can be crippling to research. Stigma associated with HIV has had a significant role in the ability to recruit and retain eligible study subjects for a nutrition based HIV study, Increasing Animal Source Foods in Diets of HIV-infected Kenyan Women and Their Children (HNP). While this study specifically focused on HIV-infected women living in Kenya, the generalization gathered could be extrapolated to other populations. It is recommended that similar studies conduct focus groups with the study population prior to piloting, to ensure stakeholder input and an understanding of the particular challenges and concerns within a local context. Future studies should also employ individuals known in the community that the population trusts to assist with recruitment. Finally, factors that identify study staff, or associate subjects with the study should be minimal to reduce the risk of disclosing a subject’s HIV status.This publication was made possible through support provided by the Office of Agriculture, Bureau of Economic Growth, Agriculture and Trade, under Grant No. PCE-G-00-98-00036-00 to University of California, Davis. The opinions expressed herein are those of the authors and do not necessarily reflect the views of USAID

Comparison of the Sequential Organ Failure Assessment (SOFA) and Quick SOFA Scores in Predicting in-Hospital Mortality among Adult Critical Care Patients with Suspected Infection

Introduction: Sepsis is global health priority and the leading cause of death in critical care. The SEPSIS 3 criteria introduced in 2016 is the latest tool in diagnosing sepsis. It uses SOFA and qSOFA scores in place of the SIRS criteria for better ability to predict mortality in patients with suspected infections. The performance of these scores in critical care units outside high-income countries remains largely unknown. Methods: We compared the performance of SOFA and qSOFA in predicting the in-hospital mortality of an adult critical care unit in Kenya. We conducted a retrospective review of all patients admitted to the critical care units with suspected infection between 1 January 2017 and 31 December 2017. A standardized electronic data collection tool was be used to collect demographic, clinical and outcome data on the participants. Area under the receiver operating characteristic curves (AUROC) with 95% confidence intervals was used to compare SOFA and qSOFA. Results: We enrolled 450 patients with a mean age of 56 years [SD ± 19.10] and 57.60% were male. Majority of the patients, 352 (78.20%), presented through the emergency department. Pneumonia was the commonest source of infection 293 (65.10%). There were 92 deaths (mortality rate of 20.44%). The majority of patients, 371 (82.44%) manifested a SOFA score of ≥ 2 and 190 (42.22%) had a qSOFA score of ≥ 2. SOFA score was superior in predicting in hospital mortality compared to qSOFA with an AUROC = 0.799 [0.752-0.846] vs. 0.694 [0.691-0.748, P \u3c 0.001]. Conclusion: A SOFA score of two or more is better than qSOFA score in predicting in-hospital mortality among adult critical care patients with suspected infection. This finding suggests that SOFA is an appropriate tool in the initial diagnosis sepsis in critical care setting in a developing country

Stroke types, risk factors, quality of care and outcomes at a Referral Hospital in Western Kenya

Background: The prevalence of stroke is increasing in sub-Saharan Africa due to increases in size of  aging population and stroke risk factors.We assessed risk factors, quality of care and outcomes of stroke to identify modifiable risk factors and areas of care that need improvement for better outcomes.Objectives: To describe the stroke types, risk factors, outcomes and stroke quality of care in a large academic medical centre hospital.Design: Hospital based retrospective study.Setting: Moi Teaching and Referral Hospital (MTRH), Eldoret, Kenya.Subjects: All patients >18 years admitted with a diagnosis of stroke as per the WHO definition and with a supporting brain imaging (CT scan/ MRI )were included in the study. Data abstracted from the files included demographic details, stroke subtype, stroke risk factors, inpatient stroke care quality  indicators(based on US Joint Commission stroke quality indicator definitions) and in hospital stroke  outcomes. Descriptive statistics was used to summarise the data.Results: A total of 155 patients had stroke between January 2010 and December 2014 of whom 42% were male, the median age was 61 (IQR: 49-72) years. Majority (73%) had hypertension. The prevalence of diabetes was 4%. Left hemiplegia/hemiparesis was the predominant presentation (50%). Haemorrhagic strokes were frequent (52%) with anterior circulation stroke comprising 97% of all strokes. Assessment of quality of care indicators showed that overall, 84% of the patients had a brain CT scan on day one of admission,93% had a GCS documented at admission, 32% were on statins and 3% were screened for dysphagia before oral intake. Among patients with ischaemic strokes; none underwent thrombolysis, 24% received DVT prophylaxis, 54% received statins, and 73% received anti-thrombotic therapy by hospital day two. In hospital mortalityoccurred in 43(27%)with a higher rate among haemorrhagic strokes (31%) compared to ischaemic stroke (24%)(p=0.364).Conclusion: Haemorrhagic stroke was the most common type of stroke admitted, hypertension was the predominant risk factor and most strokes involved the anterior circulation. In-hospital mortality was 27%.There were several opportunities to improve evidence-based quality of care indicators

Research Brief 08-02-HNP

Preliminary evidence suggests that improved nutrition early in human immunodeficiency virus (HIV) infection may delay progression to acquired immunodeficiency syndrome (AIDS) and delay the initiation or improve the effectiveness of antiretroviral drug therapy (ART). The scientific community has evolved in its appreciation of the value of food as an integral component of comprehensive care for individuals with HIV infection and AIDS. It is now well recognized that those who are food insecure and malnourished are more likely to fail drug treatment regimens. Body mass index (BMI) < 18 at the initiation of ART is strongly predictive of death. In addition, weight loss during the first four weeks of ART is also associated with death. A higher BMI is protective and is associated with better responses with ART. Patient response to nutrition intervention, however, may be confounded by the stage of HIV progression and other infections. That is, those who are in the earlier stages of the disease may respond better to aggressive nutrition intervention. The HIV Nutrition Project (HNP), "Increasing Animal Source Foods in Diets of HIV-infected Kenyan Women and Their Children," will evaluate the effect of protein quality and micronutrients found in meat on the health and nutritional well-being of women living with HIV in rural Kenya and the health and development of their children. By means of a randomized nutrition feeding intervention, researchers will study if the inclusion of meat added as an ingredient to a biscuit, when compared to soy or wheat, will best protect the immune system and prevent severe infection, prevent the loss of body mass and enhance the quality of life. These women are not yet receiving antiretroviral drugs and therefore not yet experiencing metabolic inefficiencies associated with AIDS.This publication was made possible through support provided by the Office of Agriculture, Bureau of Economic Growth, Agriculture and Trade, under Grant No. PCE-G-00-98-00036-00 to University of California, Davis. The opinions expressed herein are those of the authors and do not necessarily reflect the views of USAID

Symptom screen: diagnostic usefulness in detecting pulmonary tuberculosis in HIV-infected pregnant women in Kenya

OBJECTIVE: To determine the diagnostic usefulness of tuberculosis (TB) symptom screening to detect active pulmonary TB among human immunodeficiency virus (HIV) infected pregnant women in two PMTCT (prevention of mother-to-child transmission) clinics in western Kenya that are supported by the United States Agency for International Development–Academic Model Providing Access to Healthcare partnership. DESIGN: Cross-sectional study. Participants were interviewed for TB symptoms with a standardized questionnaire (cough >2 weeks, fever, night sweats, weight loss or failure to gain weight). Those with cough submitted sputum specimens for smear microscopy for acid-fast bacilli and mycobacterial culture. Women at >14 weeks gestation underwent shielded chest radiography (CXR). RESULTS: Of 187 HIV-infected women, 38 (20%) were symptom screen-positive. Of these, 21 had a cough for >2 weeks, but all had negative sputum smears and mycobacterial cultures. CXRs were performed in 26 symptomatic women: three were suggestive of TB (1 miliary, 1 infiltrates and 1 cavitary). Of 149 women with a negative symptom screen, 100 had a CXR and seven had a CXR suggestive of TB (1 cavitary, 2 miliary and 4 infiltrates). CONCLUSION: This study did not support the utility of isolated symptom screening in identification of TB disease in our PMTCT setting. CXR was useful in identification of TB suspects in both symptomatic and asymptomatic women

Research Brief 08-03-HNP

In sub-Saharan Africa, an estimated 28 million people are living with the human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). In 2001, Moi University in Eldoret, Kenya joined with Kenya’s second national referral hospital, Moi Teaching and Referral Hospital (MTRH) and Indiana University (IU) to establish the Academic Model Providing Access To Healthcare (AMPATH). AMPATH’s missions were to (1) provide high-quality patient care; (2) educate patients and health care providers; and (3) establish a laboratory for clinical research in HIV/AIDS (http://medicine.iupui.edu/kenya/hiv.aids.html). Leveraging the power of an academic medical partnership, AMPATH has quickly become one of the largest and most comprehensive HIV/AIDS control systems in sub-Saharan Africa, providing a comprehensive system of care that has been described as a model of sustainable development (Tobias, 2006). Delivery of services occurs in the public sector through hospitals and health centers run by Kenya’s Ministry of Health. AMPATH currently implements prevention activities that touch the lives of millions of persons in a wide geographic area. The research arm of AMPATH, created to facilitate and manage the international research agenda being generated by Kenyan and US faculty, includes the Global Livestock CRSP’s HIV Nutrition Project (HNP), “Increasing Animal Source Foods in Diets of HIV-infected Kenyan Women and Their Children,” which is a collaborative initiative between AMPATH and faculty from Moi University, Indiana University and the University of California, Los Angeles.This publication was made possible through support provided by the Office of Agriculture, Bureau of Economic Growth, Agriculture and Trade, under Grant No. PCE-G-00-98-00036-00 to University of California, Davis. The opinions expressed herein are those of the authors and do not necessarily reflect the views of USAID

Research Brief 08-01-HNP

Many of the 28 million people with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) estimated to be living in sub-Saharan Africa also suffer from malnutrition. Reproductive-aged women, their infants and young children are among the most vulnerable to malnutrition and progression of HIV to AIDS. As seen in eastern and southern Africa, mortality is increased in the malnourished. The HIV Nutrition Project (HNP) researchers will be evaluating the effect of protein quality and micronutrients found in meat on the health and nutritional well-being of women living with HIV in rural Kenya and the health and development of their children. By means of a randomized nutrition feeding intervention, the study will determine if meat in the diets of HIV-infected women and their children (1) protects the immune system and prevents severe infection, (2) prevents the loss of lean body mass, enhancing the quality of life among these drug naive women and enabling women to carry out their activities of daily living, and (3) supports the growth and development of their vulnerable children when compared to those given supplements with the same amount of energy, but with either soya or wheat protein. The intervention food with beef protein provides significantly more vitamin B12, lysine and bio-available iron and zinc when compared to the soya and wheat supplements. Deficiencies of these nutrients may hasten HIV disease progression.This publication was made possible through support provided by the Office of Agriculture, Bureau of Economic Growth, Agriculture and Trade, under Grant No. PCE-G-00-98-00036-00 to University of California, Davis. The opinions expressed herein are those of the authors and do not necessarily reflect the views of USAID

Morbidity and nutrition status of rural drug-naïve Kenyan women living with HIV

This paper describes morbidity in a group of HIV-positive drug-naïve rural women in western Kenya. A total of 226 drug-naïve HIV-positive women were evaluated for baseline morbidity, immune function, and anthropometry before a food-based nutrition intervention. Kenyan nurses visited women in their homes and conducted semi-structured interviews regarding symptoms and physical signs experienced at the time of the visit and during the previous week and physical inspection. Blood and urine samples were examined for determination of immune function (CD4, CD8, and total lymphocyte counts), anaemia, malaria, and pregnancy status. Intradermal skin testing with tuberculin (PPD), candida, and tetanus toxoid antigens was also performed to evaluate cell-mediated immunity. Anthropometry was measured, and body mass index (BMI) was calculated. Seventy-six per cent of the women reported being sick on the day of the interview or within the previous week. Illnesses considered serious were reported by 13.7% of women. The most frequent morbidity episodes reported were upper respiratory tract infections (13.3%), suspected malaria (5.85%), skeletal pain (4.87%), and stomach pain (4.42%). The most common morbidity signs on physical inspection were respiratory symptoms, most commonly rhinorrhea and coughing. Confirmed malaria and severe diarrhea were significantly associated with a higher BMI