Performance evaluation of SARS-CoV-2 rapid diagnostic tests in Nigeria: A cross-sectional study.

The COVID-19 pandemic challenged health systems globally. Reverse transcription polymerase chain reaction (RT-PCR) is the gold standard for detecting the presence of SARS-CoV-2 in clinical samples. Rapid diagnostic test (RDT) kits for COVID-19 have been widely used in Nigeria. This has greatly improved test turnover rates and significantly decreased the high technical demands of RT-PCR. However, there is currently no nationally representative evaluation of the performance characteristics and reliability of these kits. This study assessed the sensitivity, specificity, and predictive values of ten RDT kits used for COVID-19 testing in Nigeria. This large multi-centred cross-sectional study was conducted across the 6 geo-political zones of Nigeria over four months. Ten antigen (Ag) and antibody (Ab) RDT kits were evaluated, and the results were compared with RT-PCR. One thousand, three hundred and ten (1,310) consenting adults comprising 767 (58.5%) males and 543 (41.5%) females participated in the study. The highest proportion, 757 (57.7%), were in the 20-39 years' age group. In terms of diagnostic performance, Lumira Dx (61.4, 95% CI: 52.4-69.9) had the highest sensitivity while MP SARS and Panbio (98.5, 95% CI: 96.6-99.5) had the highest specificity. For predictive values, Panbio (90.7, 95% CI: 79.7-96.9) and Lumira Dx (81.2, 95% CI: 75.9-85.7) recorded the highest PPV and NPV respectively. Ag-RDTs had better performance characteristics compared with Ab-RDTs; however, the sensitivities of all RDTs in this study were generally low. The relatively high specificity of Ag-RDTs makes them useful for the diagnosis of infection in COVID-19 suspected cases where positive RDT may not require confirmation by molecular testing. There is therefore the need to develop RDTs in-country that will take into consideration the unique environmental factors, interactions with other infectious agents, and strains of the virus circulating locally. This may enhance the precision of rapid and accurate diagnosis of COVID-19 in Nigeria.

Cost-effectiveness of COVID rapid diagnostic tests for patients with severe/critical illness in low- and middle-income countries: A modeling study.

BACKGROUND: Rapid diagnostic tests (RDTs) for coronavirus disease (COVID) are used in low- and middle-income countries (LMICs) to inform treatment decisions. However, to date, it is unclear when this use is cost-effective. Existing analyses are limited to a narrow set of countries and uses. The aim of this study is to assess the cost-effectiveness of COVID RDTs to inform the treatment of patients with severe illness in LMICs, considering real world practice. METHODS AND FINDINGS: We assessed the cost-effectiveness of COVID testing across LMICs using a decision tree model, differentiating results by country income level, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) prevalence, and testing scenario (none, RDTs, polymerase chain reaction tests-PCRs and combinations). LMIC experts defined realistic care pathways and treatment options. Using a healthcare provider perspective and net monetary benefit approach, we assessed both intended (COVID symptom alleviation) and unintended (treatment side effects) health and economic impacts for each testing scenario. We included the side effects of corticosteroids, which are often the only available treatment for COVID. Because side effects depend both on the treatment and the patient's underlying illness (COVID or COVID-like illnesses, such as influenza), we considered the prevalence of COVID-like illnesses in our analyses. We found that SARS-CoV-2 testing of patients with severe COVID-like illness can be cost-effective in all LMICs, though only in some circumstances. High influenza prevalence among suspected COVID cases improves cost-effectiveness, since incorrectly provided corticosteroids may worsen influenza outcomes. In low- and some lower-middle-income countries, only patients with a high index of suspicion for COVID should be tested with RDTs, while other patients should be presumed to not have COVID. In some lower-middle-income and upper-middle-income countries, suspected severe COVID cases should almost always be tested. Further, in these settings, negative test results in patients with a high initial index of suspicion should be confirmed through PCR and, during influenza outbreaks, positive results in patients with a low initial index of suspicion should also be confirmed with a PCR. The use of interleukin-6 receptor blockers, when supported by testing, may also be cost-effective in higher-income LMICs. The cost at which they would be cost-effective in low-income countries ($162 to $406 per treatment course) is below current prices. The primary limitation of our analysis is substantial uncertainty around some of the parameters in our model due to limited data, most notably on current COVID mortality with standard of care, and insufficient evidence on the impact of corticosteroids on patients with severe influenza. CONCLUSIONS: COVID testing can be cost-effective to inform treatment of LMIC patients with severe COVID-like disease. The optimal algorithm is driven by country income level and health budgets, the level of suspicion that the patient may have COVID, and influenza prevalence. Further research to better characterize the unintended effects of corticosteroids, particularly on influenza cases, could improve decision making around the treatment of those with COVID-like symptoms in LMICs.

"We usually see a lot of delay in terms of coming for or seeking care": an expert consultation on COVID testing and care pathways in seven low- and middle-income countries.

BACKGROUND: Rapid diagnostic testing may support improved treatment of COVID patients. Understanding COVID testing and care pathways is important for assessing the impact and cost-effectiveness of testing in the real world, yet there is limited information on these pathways in low-and-middle income countries (LMICs). We therefore undertook an expert consultation to better understand testing policies and practices, clinical screening, the profile of patients seeking testing or care, linkage to care after testing, treatment, lessons learnt and expected changes in 2023. METHODS: We organized a qualitative consultation with ten experts from seven LMICs (India, Indonesia, Malawi, Nigeria, Peru, South Africa, and Zimbabwe) identified through purposive sampling. We conducted structured interviews during six regional consultations, and undertook a thematic analysis of responses. RESULTS: Participants reported that, after initial efforts to scale-up testing, the policy priority given to COVID testing has declined. Comorbidities putting patients at heightened risk (e.g., diabetes) mainly relied on self-identification. The decision to test following clinical screening was highly context-/location-specific, often dictated by local epidemiology and test availability. When rapid diagnostic tests were available, public sector healthcare providers tended to rely on them for diagnosis (alongside PCR for Asian/Latin American participants), while private sector providers predominantly used polymerase chain reaction (PCR) tests. Positive test results were generally taken at 'face value' by clinicians, although negative tests with a high index of suspicion may be confirmed with PCR. However, even with a positive result, patients were not always linked to care in a timely manner because of reluctance to receiving care or delays in returning to care centres upon clinical deterioration. Countries often lacked multiple components of the range of therapeutics advised in WHO guidelines: notably so for oral antivirals designed for high-risk mild patients. Severely ill patients mostly received corticosteroids and, in higher-resourced settings, tocilizumab. CONCLUSIONS: Testing does not always prompt enhanced care, due to reluctance on the part of patients and limited therapeutic availability within clinical settings. Any analysis of the impact or cost-effectiveness of testing policies post pandemic needs to either consider investment in optimal treatment pathways or constrain estimates of benefits based on actual practice.

"We usually see a lot of delay in terms of coming for or seeking care": an expert consultation on COVID testing and care pathways in low- and middle-income countries.

Background: Rapid diagnostic testing may support improved treatment of COVID patients. Understanding COVID testing and care pathways is important for assessing the impact and cost-effectiveness of testing in the real world, yet there is limited information on these pathways in low-and-middle income countries (LMICs). We therefore undertook an expert consultation to better understand testing policies and practices, clinical screening, the profile of patients seeking testing or care, linkage to care after testing, treatment, lessons learnt and expected changes in 2023 in LMICs. Methods: We organized a qualitative consultation with ten experts from seven LMICs identified through purposive sampling. We conducted structured interviews during six regional consultations, and undertook a thematic analysis of the responses to our questions. Results: Participants reported that, after initial efforts to scale-up testing (which often encountered delays), the policy priority given to COVID testing has declined. Comorbidities putting patients at heightened risk (e.g., diabetes) mainly relied on self-identification. The decision to test following clinical screening was highly context- and location-specific, often dictated by local epidemiology and test availability. When rapid diagnostic tests were available, public sector healthcare providers tended to rely on them for diagnosis, while private sector providers predominantly used polymerase chain reaction (PCR) tests. Positive test results were generally taken at 'face value' by clinicians, although negative tests with a high index of suspicion may be confirmed with PCR. However, even with a positive result, patients were not always linked to care in a timely manner because of reluctance to receiving care or delays in returning to care centres upon clinical deterioration. Countries often lacked multiple components of the range of therapeutics advised in WHO guidelines: notably so for oral antivirals designed for high-risk mild patients. Severely ill patients mostly received corticosteroids and, in higher-resourced settings, tocilizumab. Conclusions: Testing does not always prompt enhanced care, due to reluctance on the part of patients and limited therapeutic availability within clinical settings. Any analysis of the impact or cost-effectiveness of testing policies post pandemic needs to either consider investment in optimal treatment pathways or constrain estimates of benefits based on actual practice.

Pooling sputum testing to diagnose tuberculosis using xpert MTB/RIF and xpert ultra: a cost-effectiveness analysis.

BACKGROUND: The World Health Organization (WHO) recommends the diagnosis of tuberculosis (TB) using molecular tests, such as Xpert MTB/RIF (MTB/RIF) or Xpert Ultra (Ultra). These tests are expensive and resource-consuming, and cost-effective approaches are needed for greater coverage. METHODS: We evaluated the cost-effectiveness of pooling sputum samples for TB testing by using a fixed amount of 1,000 MTB/RIF or Ultra cartridges. We used the number of people with TB detected as the indicator for cost-effectiveness. Cost-minimization analysis was conducted from the healthcare system perspective and included the costs to the healthcare system using pooled and individual testing. RESULTS: There was no significant difference in the overall performance of the pooled testing using MTB/RIF or Ultra (sensitivity, 93.9% vs. 97.6%, specificity 98% vs. 97%, p-value > 0.1 for both). The mean unit cost across all studies to test one person was 34.10 international dollars for the individual testing and 21.95 international dollars for the pooled testing, resulting in a savings of 12.15 international dollars per test performed (35.6% decrease). The mean unit cost per bacteriologically confirmed TB case was 249.64 international dollars for the individual testing and 162.44 international dollars for the pooled testing (34.9% decrease). Cost-minimization analysis indicates savings are directly associated with the proportion of samples that are positive. If the TB prevalence is ≥ 30%, pooled testing is not cost-effective. CONCLUSION: Pooled sputum testing can be a cost-effective strategy for diagnosis of TB, resulting in significant resource savings. This approach could increase testing capacity and affordability in resource-limited settings and support increased testing towards achievement of WHO End TB strategy.

Fujifilm SILVAMP TB-LAM for the Diagnosis of Tuberculosis in Nigerian Adults.

There is a need for diagnostics for tuberculosis (TB) that are easy to use, able to screen non-sputum samples, and able to provide rapid results for the management of both immunocompromised and immunocompetent individuals. The Fujifilm SILVAMP TB LAM (FujiLAM) assay, a new non-sputum based point of need test for the diagnosis of TB, could potentially address most of these needs. We evaluated the performance of FujiLAM in HIV positive and HIV negative patients with presumptive TB attending three district hospitals in Nigeria. Consecutive patients were asked to provide urine samples on the spot, which were tested with FujiLAM. The results were compared against a positive culture and/or Xpert MTB/RIF as the reference standard. Forty-five patients had bacteriologically confirmed TB, and 159 had negative culture and Xpert MTB/RIF (no TB). The FujiLAM test was positive in 23 (sensitivity 65.7%, 95% CI = 48-80) HIV negative and seven (70%, 95% CI = 35-92) HIV positive patients with bacteriological confirmation of TB. FujiLAM was negative in 97 (specificity 99.0%, 95% CI = 94-100) HIV negative and 56 (93.3%, 95% CI = 83-98) HIV positive patients without TB. The FujiLAM test has good diagnostic accuracy for considering its application in both HIV positive and HIV negative patients with TB.

Systematic Review of Pooling Sputum as an Efficient Method for Xpert MTB/RIF Tuberculosis Testing during the COVID-19 Pandemic.

GeneXpert-based testing with Xpert MTB/RIF or Ultra assays is essential for tuberculosis diagnosis. However, testing may be affected by cartridge and staff shortages. More efficient testing strategies could help, especially during the coronavirus disease pandemic. We searched the literature to systematically review whether GeneXpert-based testing of pooled sputum samples achieves sensitivity and specificity similar to testing individual samples; this method could potentially save time and preserve the limited supply of cartridges. From 6 publications, we found 2-sample pools using Xpert MTB/RIF had 87.5% and 96.0% sensitivity (average sensitivity 94%; 95% CI 89.0%-98.0%) (2 studies). Four-sample pools averaged 91% sensitivity with Xpert MTB/RIF (2 studies) and 98% with Ultra (2 studies); combining >4 samples resulted in lower sensitivity. Two studies reported that pooling achieved 99%-100% specificity and 27%-31% in cartridge savings. Our results show that pooling may improve efficiency of GeneXpert-based testing.

PrimeStore MTM and OMNIgene Sputum for the Preservation of Sputum for Xpert MTB/RIF Testing in Nigeria.

BACKGROUND: Xpert MTB/RIF (GX) for tuberculosis (TB) diagnosis is often located in reference laboratories, and sputum needs to be transported using a cold chain. Transport media to preserve sputum are available, but performance data under programmatic conditions are limited. METHODS: Sputum samples were collected from patients with presumptive TB in Nigeria. One sputum was transported in a cold chain, tested immediately with GX and cultured. One sputum was swabbed and stored in PrimeStore-Molecular-Transport-Medium (Primestore), and the remainder was stored in OMNIGene-sputum (Omnigene), kept for seven days and tested with GX. RESULTS: Of 248 patients, 63 were fresh-sputum culture-positive and 56 GX-positive (sensitivity 88.9%, 95% CI: 78.4-95.4%). Four of 185 culture-negative patients were GX-positive (specificity 97.8%, 94.6-99.4%). Omnigene GX and Primestore GX were positive in 56/62 (90.3%, 80.1-96.4%) and 49/62 (79.0%, 66.8-88.3%) culture-positive, respectively, and 1/185 (99.5%, 97.0-100.0%) and 3/185 (98.4%, 95.3-99.7%) were culture-negative patients. 14 Human Immunodeficiency Virus (HIV)-infected and 44 HIV-uninfected patients were culture-positive. Omnigene and Primestore detected 12/14 (85.7%, 57.2-98.2%) and 5/14 (35.7%, 12.8-64.9%) HIV-infected and 41/44 (93.2%, 81.3-98.6%) HIV-uninfected culture-positive patients. Interpretation: Omnigene stored and fresh sputum samples had similar GX results. The GX results of Primestore-stored samples were similar to those found in the fresh sputum of non-HIV infected patients, but GX-positivity was lower in HIV-infected patients. This was likely due to the lower amount of bacilli collected by the swab and transferred to PrimeStore.

Genetic characterization of Mycobacterium tuberculosis complex isolates circulating in Abuja, Nigeria.

OBJECTIVE: Nigeria ranks fourth among the high tuberculosis (TB) burden countries. This study describes the prevalence of drug resistance and the genetic diversity of Mycobacterium tuberculosis in Abuja's Federal Capital Territory. MATERIALS AND METHODS: Two hundred and seventy-eight consecutive sputum samples were collected from adults with presumptive TB during 2013-2014. DNA was extracted from Löwenstein-Jensen cultures and analyzed for the identification of nontuberculous mycobacteria species, detection of drug resistance with line probe assays, and high-throughput spacer oligonucleotide typing (spoligotyping) using microbead-based hybridization. RESULTS: Two hundred and two cultures were positive for M. tuberculosis complex, 24 negative, 38 contaminated, and 15 positive for nontuberculous mycobacteria. Five (2.5%) M. tuberculosis complex isolates were resistant to rifampicin (RIF) and isoniazid (multidrug resistant), nine (4.5%) to RIF alone, and 15 (7.4%) to isoniazid alone; two RIF-resistant isolates were also resistant to fluoroquinolones and ethambutol, and one multidrug resistant isolate was also resistant to ethambutol. Among the 180 isolates with spoligotyping results, 164 (91.1%) were classified as lineage 4 (Euro-American), 13 (7.2%) as lineage 5 (West African 1), two (1.1%) as lineage 2 (East Asia), and one (0.6%) as lineage 6 (West African 2). One hundred and fifty-six (86.7%) isolates were grouped in 17 clusters (2-108 isolates/cluster), of which 108 (60.0%) were grouped as L4.6.2/Cameroon (spoligotype international type 61). CONCLUSION: The description of drug resistance prevalence and genetic diversity of M. tuberculosis in this study may be useful for improving TB control in Nigeria.

Tuberculosis and diabetes in Nigerian patients with and without HIV.

BACKGROUND: Type 2 diabetes mellitus (DM) and HIV increase the risk of tuberculosis (TB). The frequency of DM among patients with TB with and without HIV is poorly documented in many low- and middle-income countries. METHODS: This was a cross-sectional hospital-based study performed in Abuja, Nigeria. Adults with presumptive TB were screened consecutively. Sputum culture was used for TB screening and blood was used for HIV screening, as well as fasting plasma glucose (FPG) and glycated haemoglobin (HbA1c) assessment for the diagnosis of DM. HbA1c was measured using the D-10 Haemoglobin Testing System and a point-of-care test (A1C Now+ system) for comparison. Patients were classified as having DM or pre-diabetes using the D-10 reference test. RESULTS: Four hundred and ten individuals had TB culture, FPG, and HbA1c results. Participants had a mean (±standard deviation) age of 37.8±12.6 years and 217 (54.8%) were male. One hundred and thirteen (27.6%) patients were culture-positive, 62 (15.1%) had DM, and 46 (11.2%) had pre-diabetes. One hundred and eighty-four (53.3%) participants were HIV-positive and 95 (51.6%) were on antiretroviral therapy (ART). Patients with pre-diabetes and DM were more likely to have TB (odds ratio (OR) 1.94, 95% confidence interval (CI) 0.01-3.74, and OR 2.39, 95% CI 1.35-4.24, respectively). After adjustment for HIV, age, and sex, only DM was statistically associated with TB (adjusted OR (AOR) 3.10, 95% CI 1.62-5.94). HIV-negative patients with DM had a higher risk of TB (AOR 4.32, 95% CI 1.57-11.92) than HIV-positive patients with DM (AOR 3.31, 95% CI 1.29-8.54), but the difference was not statistically significant. A1C Now+ HbA1c measurements correlated poorly with the D-10 HbA1c reference test. CONCLUSION: A high proportion of patients in Abuja have markers of DM and pre-diabetes at the time of TB diagnosis.