Clinical Performance of Self-Collected Nasal Swabs and Antigen Rapid Tests for SARS-CoV-2 Detection in Resource-Poor Settings.

Background: In resource-poor countries, antigen-based rapid tests (Ag-RDTs) performed at primary healthcare and community settings improved access to SARS-CoV-2 diagnostics. However, the technical skills and biosafety requirements inherent to nasopharyngeal and oropharyngeal (OP) specimens limit the scale-up of SARS-CoV-2 testing. The collection of nasal-swabs is programmatically viable, but its performance has not been evaluated in resource-poor settings. Methods: We first evaluated the performance of SteriPack self-collected nasal swabs for the detection of SARS-CoV-2 by real-time PCR in 1498 consecutively enrolled patients with suspected infection. Next, we evaluated the clinical performance of three nasal swab-based Ag-RDTs against real-time PCR on OP specimens. Results: The sensitivity of nasal swabs was 80.6% [95% CI: 75.3−85.2%] compared to OP specimens. There was a good correlation (r = 0.58; p < 0.0001) between Ct values of 213 positive cases obtained using nasal and OP swabs. Our findings show sensitivities of 79.7% [95% CI: 73.3−85.1%] for Panbio COVID-19 Ag-RDT, 59.6% [95% CI: 55.2−63.8%] for COVIOS Ag-RDT, and 78.0% [95% CI: 73.5−82.0%] for the LumiraDx SARS-CoV-2 Ag-RDT. Conclusions: In our setting, the COVIOS Ag-RDT did not meet WHO requirements. Nasal swab-based Ag-RDTs for SARS-CoV-2 detection constitute a viable and accurate diagnostic option in resource-poor settings.

Performance Evaluation of the STANDARDTM Q COVID-19 and PanbioTM COVID-19 Antigen Tests in Detecting SARS-CoV-2 during High Transmission Period in Mozambique.

(1) Background: Laboratory-based molecular assays are the gold standard to detect SARS-CoV-2. In resource-limited settings, the implementation of these assays has been hampered by operational challenges and long turnaround times. Rapid antigen detection tests are an attractive alternative. Our aim is to evaluate the clinical performance of two SARS-CoV-2 rapid antigen tests during a high transmission period. (2) Methods: A total of 1277 patients seeking SARS-CoV-2 diagnosis were enrolled at four health facilities. Nasopharyngeal swabs for rapid antigen and real time PCR testing were collected for each patient. Sensitivity, specificity, positive and negative predictive values, misclassification rate, and agreement were determined. (3) Results: The overall sensitivity of Panbio COVID-19 was 41.3% (95% CI: 34.6-48.4%) and the specificity was 98.2% (95% CI: 96.2-99.3%). The Standard Q had an overall sensitivity and specificity of 45.0% (95% CI: 39.9-50.2%) and 97.6% (95% CI: 95.3-99.0%), respectively. The positive predictive value of a positive test was 93.3% and 95.4% for the Panbio and Standard Q Ag-RDTs, respectively. A higher sensitivity of 43.2% and 49.4% was observed in symptomatic cases for the Panbio and Standard Q Ag-RDTs, respectively. (4) Conclusions: Despite the overall low sensitivity, the two evaluated rapid tests are useful to improve the diagnosis of symptomatic SARS-CoV-2 infections during high transmission periods.

Inpatient Point-of-Care HIV Early Infant Diagnosis in Mozambique to Improve Case Identification and Linkage to Antiretroviral Therapy.

INTRODUCTION: Novel approaches to case identification and linkage to antiretroviral therapy (ART) are needed to close gaps in early infant diagnosis (EID) of HIV. Point-of-care (POC) EID is a recent innovation that eliminates the long turnaround times of conventional EID that limit patient management in the inpatient setting. The initial deployment of POC EID in Mozambique focused primarily on outpatient clinics; however, 2 high-volume tier-4 pediatric referral hospitals were also included. METHODS: To assess the impact of inpatient POC EID, a retrospective review of testing and care data from Hospital Central de Beira (HCB) and Hospital Central de Maputo (HCM) was performed for the period September 2017 to July 2018, with comparison to the 8-month pre-POC period when dried blood spots were used for conventional EID. RESULTS: Monthly testing volume increased from 8.5 tests pre-POC to 17.6 tests with POC (P<.001). Among 511 children with POC testing, the median age was 5 months, there was ongoing breastfeeding in 326 (63.8%), and 136 (26.6%) of mothers and 146 (28.6%) of infants had not received ART or antiretroviral prophylaxis, respectively. POC tests were positive in 152 (29.7%) infants, and 52 (37.5%) had a previous negative DNA polymerase chain reaction through the conventional outpatient EID program. Linkage to ART for infants with HIV-positive tests improved 64% during the POC period (P=.002). Inpatient mortality for infected infants during the POC period was 28.2%. Excluding these deaths, 61.2% of eligible infants initiated ART as inpatients, but only 29.8% of those discharged without ART were confirmed to have initiated as outpatients. CONCLUSIONS: Inpatient wards are a high-yield site for EID and ART initiation that have historically been overlooked in programming for prevention of mother-to-child transmission. POC platforms represent a transformative opportunity to increase inpatient testing, make definitive diagnoses, and improve timely linkage to ART. Scale-up plans should prioritize pediatric wards.

Performance of a True Point-of-Care Assay for HIV-1/2 Viral Load Measurement at Antenatal and Postpartum Services.

BACKGROUND: Timely viral load (VL) results during pregnancy and the postpartum period are crucial for HIV disease management and for preventing mother-to-child transmission. Point-of-care (POC) VL testing could reduce turnaround times and streamline patient management. We evaluated the diagnostic performance of the novel m-PIMA HIV-1/2 VL assay (Abbott, Chicago, IL) in Mozambique. SETTING: The study was conducted in prenatal and postpartum consultation rooms in 2 primary health care clinics. Sample collection and testing on m-PIMA were performed by trained nurses. METHODS: HIV-infected pregnant and postpartum women on antiretroviral treatment (ART) or ART naive were tested using both on-site m-PIMA POC and referral laboratory-based real-time VL assays. Linear regression analysis and Bland-Altman plots were used to calculate the agreement between both. FINDINGS: Correlation between venous blood plasma POC and plasma laboratory-based VL was strong (r2 = 0.850, P < 0.01), with good agreement between the methods [overall bias 0.202 log copies/mL (95% CI: 0.366 to 0.772 log copies/mL)]. Using the threshold of 1000 copies/mL, which is used to determine ART failure, the sensitivity and specificity of the POC VL assay were 95.0% (95% CI: 91.6% to 97.3%) and 96.5% (95% CI: 94.2% to 98.0%), respectively. The correlation coefficient between the venous and capillary sample types was 0.983 (r2 = 0.966). CONCLUSIONS: On-site, nurse-performed POC VL testing is feasible and accurate in resource-limited primary health care settings. The operational challenge of plasma separation within clinics for POC testing was successfully overcome using minicentrifuges. The use of capillary blood could simplify the execution of the assay in a clinical environment.

Performance of point-of-care birth HIV testing in primary health care clinics: An observational cohort study.

BACKGROUND: Failure to timely diagnose HIV in infants is a major barrier for scaling-up paediatric antiretroviral treatment (ART). WHO recommends birth testing for earlier diagnosis and to improve test coverage, but current diagnosis takes 2-3 weeks to complete, thereby limiting the ability of care givers to provide follow-on care, especially in low-resource settings. We evaluated the benefit of implementing rapid diagnosis of HIV at birth in primary health care maternity wards in Mozambique. METHODS AND FINDINGS: Infants born to HIV-infected mothers delivering consecutively at eight primary health care clinics were tested within 24 hours of delivery using on-site POC (Alere q HIV1/2 Detect) and standard laboratory (Roche COBAS AmpliPrep/TaqMan HIV-1 qualitative assay v2.0) testing. Infants were also tested at 4-6 weeks of age with both assays. Of 2,350 HIV-exposed infants enrolled in this implementation research study, 33 tested HIV-positive at birth on both assays. Sensitivity and specificity of POC testing compared with laboratory testing at birth were 100% (95% CI 89·4-100·0) and 100% (95% CI 99·8-100·0), respectively. At 4-6 weeks of age, 61 infants were identified as HIV-positive; of these 29 (47·5%) had a positive test at birth. Testing at both birth and 4-6 weeks identified 71 HIV-positive infants compared with 61 infants by testing at 4-6 weeks alone, a 16% increase. Two infants tested positive at birth but tested HIV-negative during follow-up. CONCLUSIONS: Adding POC birth testing to the 4-6 week screen may increase access to HIV diagnosis and expedite ART initiation in primary health care settings within low resource settings. Guidance on appropriate confirmatory HIV testing algorithms for birth testing is needed.

Effect of point-of-care early infant diagnosis on antiretroviral therapy initiation and retention of patients.

OBJECTIVE: We measured the effect of point-of-care (POC) early infant HIV testing on antiretroviral therapy initiation rates and retention in care among infants in Mozambique. DESIGN: A cluster-randomized trial was conducted in 16 primary healthcare centres providing either on-site POC arm (n = 8) or referred laboratory [standard-of-care (SOC) arm; n = 8] infant HIV testing. METHODS: The primary outcomes were the proportion of HIV-positive infants initiating antiretroviral therapy within 60 days of sample collection, and the proportion of HIV-positive infants who initiated antiretroviral therapy that were retained in care at 90 days of follow-up. RESULTS: The proportion of HIV-positive infants initiating antiretroviral therapy within 60 days of sample collection was 89.7% (157 of 175) for the POC arm and 12.8% (13 of 102) for the SOC arm [relative risk (RR)(adj) 7.34; P < 0.001]. The proportion of HIV-positive infants who initiated antiretroviral therapy that were retained in care at 90 days of follow-up was 61.6% (101 of 164) for the POC arm and 42.9% (21 of 49) for the SOC arm [RR(adj) 1.40; P < 0.027]. The median time from sample collection to antiretroviral therapy initiation was less than 1 day (interquartile range: 0-1) for the POC arm and 127 days (44-154; P < 0.001) for the SOC arm. CONCLUSION: POC infant HIV testing enabled clinics to more rapidly diagnose and provide treatment to HIV-infected infants. This reduced opportunities for pretreatment loss to follow-up and enabled a larger proportion of infants to receive test results and initiate antiretroviral therapy. The benefits of faster HIV diagnosis and antiretroviral treatment may also improve early retention in care.

Early diagnosis of preeclampsia using placental growth factor: An operational pilot study in Maputo, Mozambique.

In well-resourced settings, reduced circulating maternal free placental growth factor (PlGF) aids in either predicting or confirming the diagnosis of preeclampsia, fetal growth restriction, stillbirth, preterm birth, and delivery within 14 days of testing when pre-eclampsia is suspected. This operational pilot implementation of maternal plasma PlGF in women with suspected preeclampsia was conducted in six antenatal clinics in Maputo, Mozambique (six control clinics for comparison). The primary outcome was transfer to higher levels of care, following the informative PlGF assay. Of antenatal visits, 133/31,993 (0.42%) and 20/33,841 (0.06%) resulted in pre-eclampsia-related transfers of care for women attending intervention and control clinics, respectively (p < .0001). The clinic-to-delivery for women with low PlGF (<100 pg/ml) interval was shorter, (vs normal PlGF (median 10 days [IQR 1-25] vs 36 [11-83], p < .0001)). Low PlGF was associated with younger maternal age, higher blood pressure, earlier delivery, more therapeutic interventions, preterm birth, lower birth weight, and perinatal loss. In addition, one-third of hypertensive women with PlGF < 50 pg/ml suffered a stillbirth. In urban Mozambican women with symptoms and/or signs suggestive of preeclampsia, low maternal plasma PlGF concentrations are associated with increased risks of adverse pregnancy outcomes, especially early delivery and stillbirth. Therefore, introducing PlGF into the clinical care of women with suspected preeclampsia was associated with increased transfers to higher levels of care; low PlGF (<100 pg/ml) was associated with increased maternal and perinatal risks. PlGF < 50 pg/ml is particularly associated with stillbirth in women with suspected preeclampsia.

Diagnostic Performance of Placental Growth Factor in Women With Suspected Preeclampsia Attending Antenatal Facilities in Maputo, Mozambique.

In well-resourced settings, reduced circulating maternal-free placental growth factor (PlGF) aids in either predicting or confirming the diagnosis of preeclampsia, fetal growth restriction, stillbirth, preterm birth, and delivery within 14 days of testing when preeclampsia is suspected. This blinded, prospective cohort study of maternal plasma PlGF in women with suspected preeclampsia was conducted in antenatal clinics in Maputo, Mozambique. The primary outcome was the clinic-to-delivery interval. Other outcomes included: confirmed diagnosis of preeclampsia, transfer to higher care, mode of delivery, intrauterine fetal death, preterm birth, and low birth weight. Of 696 women, 95 (13.6%) and 601 (86.4%) women had either low (<100 pg/mL) or normal (≥100 pg/mL) plasma PlGF, respectively. The clinic-to-delivery interval was shorter in low PlGF, compared with normal PlGF, women (median 24 days [interquartile range, 10-49] versus 44 [24-81], P=0.0042). Also, low PlGF was associated with a confirmed diagnosis of preeclampsia, higher blood pressure, transfer for higher care, earlier gestational age delivery, delivery within 7 and 14 days, preterm birth, cesarean delivery, lower birth weight, and perinatal loss. In urban Mozambican women with symptoms or signs suggestive of preeclampsia, low maternal plasma PlGF concentrations are associated with increased risks of adverse pregnancy outcomes, whether the diagnosis of preeclampsia is confirmed. Therefore, PlGF should improve the provision of precision medicine to individual women and improve pregnancy outcomes for those with preeclampsia or related placenta-mediated complications.