Testing programs for severe acute respiratory syndrome coronavirus 2 have relied on high-throughput polymerase chain reaction laboratory tests and rapid antigen assays to meet diagnostic needs. Both ...technologies are essential; however, issues of cost, accessibility, manufacturing delays, and performance have limited their use in low-resource settings and contributed to the global inequity in coronavirus disease 2019 testing. Emerging low-cost, multidisease point-of-care nucleic acid tests may address these limitations and strengthen pandemic preparedness, especially within primary healthcare where most cases of disease first present. Widespread deployment of these novel technologies will also help close long-standing test access gaps for other diseases, including tuberculosis, human immunodeficiency virus, cervical cancer, viral hepatitis, and sexually transmitted infections. We propose a more optimized testing framework based on greater use of point-of-care nucleic acid tests together with rapid immunologic assays and high-throughput laboratory molecular tests to improve the diagnosis of priority endemic and epidemic diseases, as well as strengthen the overall delivery of primary healthcare services.
Summary Background Loss to follow-up of HIV-positive patients before initiation of antiretroviral therapy can exceed 50% in low-income settings and is a challenge to the scale-up of treatment. We ...implemented point-of-care counting of CD4 cells in Mozambique and assessed the effect on loss to follow-up before immunological staging and treatment initiation. Methods In this observational cohort study, data for enrolment into HIV management and initiation of antiretroviral therapy were extracted retrospectively from patients' records at four primary health clinics providing HIV treatment and point-of-care CD4 services. Loss to follow-up and the duration of each preparatory step before treatment initiation were measured and compared with baseline data from before the introduction of point-of-care CD4 testing. Findings After the introduction of point-of-care CD4 the proportion of patients lost to follow-up before completion of CD4 staging dropped from 57% (278 of 492) to 21% (92 of 437) (adjusted odds ratio OR 0·2, 95% CI 0·15–0·27). Total loss to follow-up before initiation of antiretroviral treatment fell from 64% (314 of 492) to 33% (142 of 437) (OR 0·27, 95% CI 0·21–0·36) and the proportion of enrolled patients initiating antiretroviral therapy increased from 12% (57 of 492) to 22% (94 of 437) (OR 2·05, 95% CI 1·42–2·96). The median time from enrolment to antiretroviral therapy initiation reduced from 48 days to 20 days (p<0·0001), primarily because of a reduction in the median time taken to complete CD4 staging, which decreased from 32 days to 3 days (p<0·0001). Loss to follow-up between staging and antiretroviral therapy initiation did not change significantly (OR 0·84, 95% CI 0·49–1·45). Interpretation Point-of-care CD4 testing enabled clinics to stage patients rapidly on-site after enrolment, which reduced opportunities for pretreatment loss to follow-up. As a result, more patients were identified as eligible for and initiated antiretroviral treatment. Point-of-care testing might therefore be an effective intervention to reduce pretreatment loss to follow-up. Funding Absolute Return for Kids and UNITAID.
Inadequate levels of immunization against childhood diseases remain a significant public health problem in resource-poor areas of the globe. Nonetheless, the reasons for incomplete vaccination and ...non-uptake of immunization services are poorly understood. This study aimed at finding out the reasons for non-vaccination and the magnitude of missed opportunities for vaccination in children less than two years of age in a rural area in southern Mozambique.
Mothers of children under two years of age (N = 668) were interviewed in a cross-sectional study. The Road-to-Health card was utilized to check for completeness and correctness of vaccination schedule as well as for identifying the appropriate use of all available opportunities for vaccination. The chi-square test and the logistic regression were used for statistical analysis.
We found that 28.2% of the children had not completed the vaccination program by two years of age, 25.7% had experienced a missed opportunity for vaccination and 14.9% were incorrectly vaccinated. Reasons for incomplete vaccination were associated with accessibility to the vaccination sites, no schooling of mothers and children born at home or outside Mozambique.
Efforts to increase vaccination coverage should take into account factors that contribute to the incomplete vaccination status of children. Missed opportunities for vaccination and incorrect vaccination need to be avoided in order to increase the vaccine coverage for those clients that reach the health facility, specially in those countries where health services do not have 100% of coverage.
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.
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.
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.
This article aims at examining the key recent advances in the field of EID, as well as at discussing approaches for resolving the major bottlenecks faced by health systems in the identification and ...linkage to care of HIV-infected infants.
Programmatic experience in South Africa and research in other high-burden countries showed that birth HIV testing is accurate, feasible and has the potential to decrease infant mortality. Substantial evidence has mounted on the accuracy of point-of-care testing for EID, including for birth testing. Importantly, it has now been demonstrated that point-of-care EID improves the rate of results return to patients and has significant positive effect on ART initiation rates. Finally, there are good examples of how EID fits into more comprehensive and integrated packages of services covering the antenatal, birth and postpartum periods.
Point-of-care testing for EID, including for birth testing, should be widely implemented to complement laboratory-based testing in high-burden countries. Most of the current barriers for timely EID testing and ART initiation in infants are related to weaknesses in the health system, and will require the implementation of comprehensive approaches aiming at scaling-up these interventions within strengthened primary healthcare services.
We used data from a randomized trial of HIV-tuberculosis co-infected patients in Mozambique to determine the incidence and predictors of paradoxical tuberculosis-associated immune reconstitution ...inflammatory syndrome (IRIS) occurring within 12 weeks of starting antiretroviral therapy, and to evaluate its association with patient outcome at 48 weeks.
HIV-tuberculosis co-infected and antiretroviral therapy-naïve adults with less than 250 CD4/mm3 were randomized to a nevirapine or efavirenz-based antiretroviral therapy initiated 4 to 6 weeks after starting tuberculosis treatment, and were then followed for 48 weeks. Tuberculosis cases were diagnosed using WHO guidelines, and tuberculosis-IRIS by case definitions of the International Network for the Study of HIV-associated IRIS.
The 573 HIV-tuberculosis co-infected patients who initiated antiretroviral therapy had a median CD4 count of 92 cells/mm(3) and HIV-1 RNA of 5.6 log10 copies/mL. Mortality at week 48 was 6.1% (35/573). Fifty-three (9.2%) patients presented a tuberculosis-IRIS within 12 weeks of starting antiretroviral therapy. Being female and having a low CD4 count, high HIV-1 RNA load, low body mass index and smear-positive pulmonary tuberculosis were independently associated with tuberculosis-IRIS. After adjustment for baseline body mass index, CD4 count and hemoglobin, occurrence of tuberculosis-IRIS was independently associated with 48-week mortality (aOR 2.72 95%CI 1.14-6.54). Immunological and HIV-1 virological responses and tuberculosis treatment outcomes were not different between patients with and without tuberculosis-IRIS.
In this large prospective cohort, tuberculosis-IRIS occurrence within 12 weeks of starting antiretroviral therapy was independently associated with the mortality of HIV-tuberculosis co-infected patients at 48 weeks post antiretroviral therapy initiation.
Point-of-care CD4 tests at HIV diagnosis could improve linkage to care in resource-limited settings. Our objective is to evaluate the clinical and economic impact of point-of-care CD4 tests compared ...to laboratory-based tests in Mozambique.
We use a validated model of HIV testing, linkage, and treatment (CEPAC-International) to examine two strategies of immunological staging in Mozambique: (1) laboratory-based CD4 testing (LAB-CD4) and (2) point-of-care CD4 testing (POC-CD4). Model outcomes include 5-y survival, life expectancy, lifetime costs, and incremental cost-effectiveness ratios (ICERs). Input parameters include linkage to care (LAB-CD4, 34%; POC-CD4, 61%), probability of correctly detecting antiretroviral therapy (ART) eligibility (sensitivity: LAB-CD4, 100%; POC-CD4, 90%) or ART ineligibility (specificity: LAB-CD4, 100%; POC-CD4, 85%), and test cost (LAB-CD4, US$10; POC-CD4, US$24). In sensitivity analyses, we vary POC-CD4-specific parameters, as well as cohort and setting parameters to reflect a range of scenarios in sub-Saharan Africa. We consider ICERs less than three times the per capita gross domestic product in Mozambique (US$570) to be cost-effective, and ICERs less than one times the per capita gross domestic product in Mozambique to be very cost-effective. Projected 5-y survival in HIV-infected persons with LAB-CD4 is 60.9% (95% CI, 60.9%-61.0%), increasing to 65.0% (95% CI, 64.9%-65.1%) with POC-CD4. Discounted life expectancy and per person lifetime costs with LAB-CD4 are 9.6 y (95% CI, 9.6-9.6 y) and US$2,440 (95% CI, US$2,440-US$2,450) and increase with POC-CD4 to 10.3 y (95% CI, 10.3-10.3 y) and US$2,800 (95% CI, US$2,790-US$2,800); the ICER of POC-CD4 compared to LAB-CD4 is US$500/year of life saved (YLS) (95% CI, US$480-US$520/YLS). POC-CD4 improves clinical outcomes and remains near the very cost-effective threshold in sensitivity analyses, even if point-of-care CD4 tests have lower sensitivity/specificity and higher cost than published values. In other resource-limited settings with fewer opportunities to access care, POC-CD4 has a greater impact on clinical outcomes and remains cost-effective compared to LAB-CD4. Limitations of the analysis include the uncertainty around input parameters, which is examined in sensitivity analyses. The potential added benefits due to decreased transmission are excluded; their inclusion would likely further increase the value of POC-CD4 compared to LAB-CD4.
POC-CD4 at the time of HIV diagnosis could improve survival and be cost-effective compared to LAB-CD4 in Mozambique, if it improves linkage to care. POC-CD4 could have the greatest impact on mortality in settings where resources for HIV testing and linkage are most limited. Please see later in the article for the Editors' Summary.
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