Six months survival and risk factors for attrition for patients detected with cryptococcal antigenemia through screening in Malawi.

MAIN OBJECTIVE: A cohort of adult Malawian people living with HIV (PLHIV) testing positive for cryptococcal antigenemia was observed and followed to determine the outcomes and risk factors for attrition. METHODS CONCEPT: Eligible PLHIV were enrolled at 5 health facilities in Malawi, representing different levels of health care. ART naïve patients, ART defaulters returning to care, and patients with suspected or confirmed ART treatment failure with CD4 <200 cells/µL or clinical stage 3 or 4 were enrolled and received CrAg tests on whole blood specimens from August 2018 to August 2019. Hospitalized PLHIV were enrolled and tested for CrAg from January 2019 to August 2019, regardless of CD4 or clinical stage. Patients with cryptococcal antigenemia were managed per Malawian clinical guidelines and were followed up for six months. Survival and risk factors for attrition at six months were assessed. RESULTS: A total of 2146 patients were screened and 112 (5.2%) had cryptococcal antigenemia. Prevalence ranged from 3.8% (Mzuzu Central Hospital) to 25.8% (Jenda Rural Hospital). Of the 112 patients with antigenemia, 33 (29.5%) were diagnosed with concurrent CM at the time of enrollment. Six-month crude survival of all patients with antigenemia (regardless of CM status) ranged from 52.3% (assuming lost-to-follow-up (LTFU) patients died) to 64.9% (if LTFU survived). Patients who were diagnosed with concurrent CM by CSF test had poor survival (27.3-39.4%). Patients with antigenemia who were not diagnosed with concurrent CM had 71.4% (if LTFU died)- 89.8% (if LTFU survived) survival at six months. In adjusted analyses, patients with cryptococcal antigenemia detected after admission to inpatient care (aHR: 2.56, 1.07-6.15) and patients with concurrent CM at the time of positive antigenemia result (aHR: 2.48, 1.04-5.92) had significantly higher hazard of attrition at six months. CONCLUSIONS: Overall, our findings indicate a need for routine access to CrAg screening and pre-emptive fluconazole treatment as a way to detect cryptococcal antigenemia and prevent CM in outpatient and inpatient settings. Rapid access to diagnosis and treatment for cryptococcal meningitis (CM) with gold-standard antifungals is needed to improve survival of patients with advanced HIV in Malawi.

Histopathological profile of orbito-ocular cancers at a tertiary hospital in Northern Malawi: a retrospective cross-sectional study.

Objective: Orbito-ocular cancers are a common cause of morbidity and mortality in our population, yet these cancers have not been adequately described in Malawi. This study sought to describe the burden and histopathological profile of orbito-ocular cancers in Northern Malawi. Methods and Analysis: A retrospective review of pathology reports was done. Descriptive analyses were performed to summarise patients' demographic and clinical characteristics, and histopathological results. A binary logistic regression was used to explore the association between demographic variables, site of lesion and cancer. Results: 210 pathology reports of orbito-ocular biopsies were reviewed. 60.0% of patients were female. The majority (39.5%) of patients were in the 31 to 40 age group but overall mean age (±SD) was 34.81±15.9 years. Cancer was diagnosed in 84 (40.0%) patients. Squamous cell carcinoma constituted the majority (82.1%) of cancers followed by retinoblastoma at 7.1%. Orbito-ocular cancers were associated with HIV infection (OR5.9, 95% CI 2.0 to 17.2) and intraocular tumours were 8.3 times (OR 8.3, 95% CI 2.0 to 33.8) more likely to be malignant. However, squamous cell carcinoma was the only type of cancer found in patients with HIV infection and mostly affected the conjunctiva, constituting 94.4% of cancers affecting this site. Retinoblastoma on the other hand only affected children less than 10 years of age. Conclusion: Cancer constituted a substantial proportion of orbito-ocular lesions in our study population, with conjunctiva being the common site. This calls for improved capacity to prevent, diagnose and manage orbito-oracular cancers in Northern Malawi and similar settings.

Histopathological profile of cervical biopsies in northern Malawi: a retrospective cross-sectional study.

OBJECTIVES: According to the WHO (2014), cervical cancer is the second most common cancer in women globally. More than 85% of the global cervical cancer morbidity and mortality occur in low-income and middle-income countries and the highest risk region is in Eastern and Southern Africa. Malawi has the highest age-standardised rate of cervical cancer in the world. This study was carried out to determine the histopathological profile of cervical biopsies in a public tertiary hospital in Mzuzu, northern region of Malawi. SETTING: A public tertiary hospital in Mzuzu, northern region of Malawi. PARTICIPANTS: This was a retrospective study of all cervical biopsy specimen reports received in a public tertiary hospital in northern Malawi over a period of 5 years from July 2013 to June 2018. Demographic, clinical and diagnostic data were obtained from original histopathology reports. RESULTS: A total of 500 cervical biopsy reports were reviewed during the study period. The mean age of the patients was 41.99±12.5. Age ranged from 15 to 80 years. Cervicitis accounted for 46.0% (n=162) of the total non-malignant lesions seen, followed by cervical intraepithelial neoplasm, at 24.4% (n=86) and endocervical polyp, at 20.5% (n=72). Squamous cell carcinoma (SCC) accounted for 15.6% (n=78) of the total cervical biopsies studied and 85.7% of all total malignant lesions. Adenocarcinoma and undifferentiated carcinoma were 8.8% and 4.4%, respectively of the total malignant diagnosis. All patients with malignant lesions had HIV. CONCLUSION: Our study shows that cervicitis and SCC were most common among non-malignant and malignant cervical biopsies, respectively. Since the frequency of cervical cancer is high, there is a need to have well detailed national policies to be put in place to increase detection of preinvasive lesions in order to reduce the prevalence of cervical cancer.

Histopathological profile of breast cancer at a tertiary hospital in Malawi: A retrospective cross-sectional study.

Breast cancer is one of the major public health problem in developing countries. In Malawi, cancer of the breast among females is among the top four accounting for 4.9%. The study determined the histopathologic profile of breast cancer in Northern Malawi from July 2013 to June 2018. A record based retrospective cross-sectional study was conducted at Mzuzu Central Hospital. We reviewed 202 histopathological results of breast specimens during the study period. Data was analyzed using STATA version 14.0. Out of 202 clinically diagnosed breast lesions/tumours, 102 (50.5%) were histopathologically confirmed cancerous in nature, and 100 (49.5%) were non-cancerous. Ductal carcinoma was the leading histologic presentation with 68 cases representing 66.7%. Participants in the age group of 70-89 years were 13 times more likely to develop breast cancer (OR 12.66; P-value = 0.001; 95% CI 2.79 - 57.46), compared to those in the age group 10-29 years. The magnitude of breast cancer in Mzuzu Central Hospital, Northern Malawi is alarming (50.5%). Policy makers should emphasise on awareness campaigns for early and routine breast screening, early diagnosis and early treatment.

A comparative evaluation of three methods for the rapid diagnosis of cryptococcal meningitis (CM) among HIV-infected patients in Northern Malawi.

Introduction: Cryptococcal meningitis (CM) is the most common systemic fungal infection in patients with HIV infection. Rapid diagnosis and timely initiation of antifungal therapy are key to reducing mortality rate associated with CM. This study aims to evaluate the ability of four different diagnostic tests (Gram stain, India ink, and two types of commercial lateral flow assay [LFA]) to identify CM-positive patients and to compare the sensitivity and specificity of these tests. Methods: This was a prospective cross-sectional study on diagnostic tests accuracy conducted in Northern Malawi. The target population was HIV-infected adult patients presenting with features of meningitis. Four types of diagnostic tests were conducted: India ink, Gram stain, and two types of commercial lateral flow assay (LFA) (Immy, Inc., OK, USA and Dynamiker Biotechnology (Tianjin) Co., Ltd), Singapore). Culture was conducted as the reference standard. Results: A total of 265 samples were collected. The rate of positive CM detection ranged from 6.4% (using India ink) to 14.3% (using LFA). India ink exhibited the lowest sensitivity of 54.8% (95% confidence interval [CI]: 36.0%-72.7%), followed by Gram stain (61.3%; 95% CI: 42.2%-78.2%). The Dynamiker LFA exhibited the highest sensitivity of 100.0% (95% CI: 90.0%-100.0%) but a lower specificity (97.0%; 93.9%-98.8%) compared to the Immy LFA (98.3%; 95% CI: 95.7%-99.5%). Conclusion: LFA diagnostic methods have the potential to double the detection rate of CM-positive patients in resource-limited countries such as Malawi. As such, LFAs should be considered to become the main diagnostic tests used for CM diagnostics in these countries. Our data indicate that LFAs may be the best method for diagnosing CM and exhibits the highest diagnostic accuracy as it has shown that it outperforms cell culture, the current gold standard.