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.

Diagnostic capacity for invasive fungal infections in advanced HIV disease in Africa: a continent-wide survey.

BACKGROUND: Fungal infections are common causes of death and morbidity in those with advanced HIV infection. Data on access to diagnostic tests in Africa are scarce. We aimed to evaluate the diagnostic capacity for invasive fungal infections in advanced HIV disease in Africa. METHODS: We did a continent-wide survey by collecting data from 48 of 49 target countries across Africa with a population of more than 1 million; for Lesotho, only information on the provision of cryptococcal antigen testing was obtained. This survey covered 99·65% of the African population. We did the survey in six stages: first, questionnaire development, adaptation, and improvement; second, questionnaire completion by in-country respondents; third, questionnaire review and data analysis followed by video conference calls with respondents; fourth, external validation from public or private sources; fifth, country validation by video conference with senior figures in the Ministry of Health; and sixth, through five regional webinars led by the Africa Centres for Disease Control and Prevention with individual country profiles exchanged by email. Data was compiled and visualised using the Quantum Geographic Information System software and Natural Earth vectors to design maps showing access. FINDINGS: Data were collected between Oct 1, 2020, and Oct 31, 2022 in the 48 target countries. We found that cryptococcal antigen testing is frequently accessible to 358·39 million (25·5%) people in 14 African countries. Over 1031·49 million (73·3%) of 1·4 billion African people have access to a lumbar puncture. India ink microscopy is frequently accessible to 471·03 million (33·5%) people in 23 African countries. About 1041·62 million (74·0%) and 1105·11 million (78·5%) people in Africa do not have access to histoplasmosis and Pneumocystis pneumonia diagnostics in either private or public facilities, respectively. Fungal culture is available in 41 countries covering a population of 1·289 billion (94%) people in Africa. MRI is routinely accessible to 453·59 million (32·2%) people in Africa and occasionally to 390·58 million (27·8%) people. There was a moderate correlation between antiretroviral therapy usage and external expenditure on HIV care (R2=0·42) but almost none between external expenditure and AIDS death rate (R2=0·18), when analysed for 40 African countries. INTERPRETATION: This survey highlights the enormous challenges in the diagnosis of HIV-associated Pneumocystis pneumonia, cryptococcal disease, histoplasmosis, and other fungal infections in Africa. Urgent political and global health leadership could improve the diagnosis of fungal infections in Africa, reducing avoidable deaths. FUNDING: Global Action For Fungal Infections.

Patient satisfaction with health care at a tertiary hospital in Northern Malawi: results from a triangulated cross-sectional study.

BACKGROUND: In 2016 the Malawi government embarked on several interrelated health sector reforms aimed at improving the quality of health services at all levels of care and attain Universal Health Coverage by 2030. Patient satisfaction with services is an important proxy measure of quality. We assessed patient satisfaction at a tertiary hospital in Northern Malawi to understand the current state. METHODS: We conducted exit interviews with patients aged ≥ 18 years using a 28 statement interviewer administered questionnaire. Patients were asked to express their level of agreement to each statement on a five-point Likert scale - strongly disagree to strongly agree, corresponding to scores of 1 to 5. Overall patient satisfaction was calculated by summing up the scores and dividing the sum by the number of statements. Mean score > 3 constituted satisfaction while mean score ≤ 3 constituted dissatisfaction. A χ2 test was used to assess the association between overall patient satisfaction and demographic variables, visit type and clinic consulted at alpha 0.05. Patient self-rated satisfaction was determined from a single statement that asked patients to rate their satisfaction with services on a five-point Likert scale. We also asked patients to mention aspects of hospital care that they did not like. Responses were summarized into major issues which are presented according to frequencies. RESULTS: Overall patient satisfaction was 8.4% (95% CI: 5.2 - 12.9%). Self-rated patient satisfaction was 8.9% (95% CI: 5.5 - 13.4%). There was no significant association between overall patient satisfaction and all predictor variables assessed. Patients raised six major issues that dampened their health care seeking experience, including health workers reporting late to work, doctors not listening to patients concerns and neither examining them properly nor explaining the diagnosis, shortage of medicines, diagnostics and medical equipment, unprofessional conduct of health workers, poor sanitation and cleanliness, and health worker behaviour of favouring relatives and friends over other patients. CONCLUSIONS: We found very low levels of patient satisfaction, suggesting that quality of services in the public health sector is still poor. It is, therefore, critical to accelerate and innovate the Ministry of Health's quality improvement initiatives to attain Malawi's health goals.

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.

Paediatric sickle cell disease at a tertiary hospital in Malawi: a retrospective cross-sectional study.

Introduction: Sickle cell disease (SCD) remains a major cause of childhood mortality and morbidity in Malawi. However, literature to comprehensively describe the disease in the paediatric population is lacking. Methods: A retrospective review of clinical files of children with SCD was conducted. Descriptive statistics were performed to summarise the data. χ2 or Fisher's exact test was used to look for significant associations between predictor variables and outcome variables (case fatality and length of hospital stay). Predictor variables that were significantly associated with outcome variables (p≤0.05) in a χ2 or Fisher's exact test were carried forward for analysis in a binary logistic regression. A multivariable binary logistic regression was used to identify covariates that independently predicted length of hospital stay. Results: There were 16 333 paediatric hospitalisations during the study period. Of these, 512 were patients with SCD representing 3.1% (95% CI: 2.9%- 3.4%). Sixty-eight of the 512 children (13.3%; 95% CI: 10.5% - 16.5%) were newly diagnosed cases. Of these, only 13.2% (95% CI: 6.2% - 23.6%) were diagnosed in infancy. Anaemia (94.1%), sepsis (79.5%) and painful crisis (54.3%) were the most recorded clinical features. The mean values of haematological parameters were as follows: haemoglobin (g/dL) 6.4 (SD=1.9), platelets (×109/L) 358.8 (SD=200.9) while median value for white cell count (×109/L) was 23.5 (IQR: 18.0-31.2). Case fatality was 1.4% (95% CI: 0.6% - 2.8%)and 15.2% (95% CI: 12.2% -18.6%) of the children had a prolonged hospital stay (>5 days). Patients with painful crisis were 1.7 (95% CI: 1.02 - 2.86) times more likely to have prolonged hospital stay than those without the complication. Conclusion: Anaemia, sepsis and painful crisis were the most common clinical features paediatric patients with SCD presented with. Patients with painful crisis were more likely to have prolonged hospital stay. Delayed diagnosis of SCD is a problem that needs immediate attention in this setting. Although somewhat encouraging, the relatively low in-hospital mortality among SCD children may under-report the true mortality from the disease considering community deaths and deaths occurring before SCD diagnosis is made.

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.

Prevalence, distribution and antimicrobial susceptibility pattern of bacterial isolates from a tertiary Hospital in Malawi.

BACKGROUND: Bacterial infections are a significant cause of sickness and death in sub-Saharan Africa. This study aimed at establishing the prevalence, distribution and antimicrobial susceptibility pattern of major bacterial isolates from patients accessing medical care at a tertiary hospital in Malawi. METHODS: We retrospectively reviewed bacteria culture and antimicrobial susceptibility records for 4617 patients from 2002 to 2014 at Mzuzu Central Hospital (MCH). No inclusion and exclusion criteria were followed. Data was analysed using excel (Microsoft office, USA) and GraphPad prism 7 software programs. RESULTS: The most prevalent isolates were S. aureus (34.7%, n = 783), Klebsiella species (17.4%, n = 393) and Proteus species (11.4%, n = 256). Most microorganisms were isolated from adults (88.3%, n = 3889) and pus was the main source (69.3%, n = 1224). S. pneumoniae was predominantly isolated from cerebrospinal fluid (60.3%, n = 44) largely collected from children (88.2%, n = 64). Overall, most bacteria exhibited high resistance to all regularly used antimicrobials excluding ciprofloxacin. CONCLUSIONS: Our report demonstrates an increase in bacterial infection burden in sites other than blood stream and subsequent increase in prevalence of antimicrobial resistance for all major isolates. Creating an epidemiological survey unit at MCH will be essential to help inform better treatment and management options for patients with bacterial infections.

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.

CD4 Variability in Malawi: Implications for Use of a CD4 Threshold of 500 Cells/mm3 Versus Universal Eligibility for Antiretroviral Therapy.

Background. Given the uncertainty about the ability of a single CD4 count to accurately classify a patient as antiretroviral therapy (ART) eligible, we sought to understand the extent to which CD4 variability results in misclassification at a CD4 threshold of 500 cells/mm3. Methods. We performed a prospective study of CD4 variability in Malawian human immunodeficiency virus-infected, ART-naive, World Health Organization (WHO) stage 1 or 2, nonpregnant adults. CD4 counts were performed daily for 8 days. We fit a Bayesian linear mixed-effects model of log-transformed CD4 cell counts to the data. We used Monte Carlo approximations to estimate misclassification rates for different observed values of CD4. The misclassification rate was calculated based on the conditional probability of true CD4 given the geometric mean of observed CD4 measurements. Results. Fifty patients were enrolled from 2 sites. The median age was 33.5 years (interquartile range, 27.5-40.0) and 34 (68%) were female. Misclassification rates were <1% when the observed CD4 counts were ≤250 or ≥750 cells/mm3. Rates of misclassification were high at observed CD4 counts between 350 and 650 cells/mm3, particularly when a single measurement was used (up to 46.7%). Conclusions. Our data show that ART eligibility based on a single CD4 count results in highest risk of misclassification when observed CD4 counts are in the range of 350-650 cells/mm3. Given the benefits of early ART, countries should weigh the costs and complexity of CD4 testing using a 500 cell/mm3 threshold against the cost savings and public health benefits of universal eligibility.