Joep Lange Institute

Background Many governments in low- and middle-income countries (LMICs) have difficulties paying healthcare costs upfront leading to high out-of-pocket payments for patients. A Development Impact Bond (DIB) is an innovative financing mechanism in which pr ivate investors provide pre-payment of development program expenses. At the same time, public agencies or donors repay the investor’s investment with a reasonable interest rate if the program succeeds in delivering independently measurable results that are contractually agreed upon. This study assessed quantitatively and qualitatively the feasibility of a DIB for hepatitis C Virus (HCV) diagnosis and treatment in Cameroon. Methods A revolving fund of up to €230,000 was made available by the investor. The outcome payor reimbursed the investor only in case of good performance, defined as cured patients (HCV-RNA negative). HCV carriers who were identified were referred for treatment and tested for cure 12 weeks after completion of treatment, the outcome being validated by an independent assessor. The evaluation was guided by the six-agents model, involving interviews with relevant stakeholders (N= 22). Results In total, 253 (98%) patients completed treatment, of which 244 (96%) are cured at week 24. We estimated that the average per-patient outcome payment for HCV diagnosis and treatment is €1,542, and the average costs per treated patient is €1,858. The investor was fully repaid, including the agreed interest and bonus. Themes or findings from the interviews confirmed the feasibility of a DIB in a low-resource setting. Conclusions This study demonstrates that a DIB can be a suitable financing mechanism for HCV services, supporting the path towards elimination. When governments in LMICs do not have sufficient resources to fund such elimination programs upfront, such public-private partnerships can offer a solution.

To evaluate the role of C-reactive protein (CRP) in predicting severe COVID-19 patients. A prospective observational cohort study was conducted from July 15 to October 28, 2020, at Kuyha COVID-19 isolation and treatment center hospital, Mekelle City, Northern Ethiopia. A total of 670 blood samples were collected serially. SARS-CoV-2 infection was confirmed by RT-PCR from nasopharyngeal swabs and CRP concentration was determined using Cobas Integra 400 Plus (Roche). Data were analyzed using STATA version 14. P-value <0.05 was considered statistically significant. Overall, COVID-19 patients had significantly elevated CRP at baseline when compared to PCR-negative controls [median 11.1 (IQR: 2.0-127.8) mg/L vs 0.9 (IQR: 0.5-1.9) mg/L; p=0.0004)]. Those with severe COVID-19 clinical presentation had significantly higher median CRP levels compared to those with non-severe cases [166.1 (IQR: 48.6-332.5) mg/L vs 2.4 (IQR: 1.2-7.6) mg/L; p<0.00001)]. Moreover, COVID-19 patients exhibited higher median CRP levels at baseline [58 (IQR: 2.0-127.8) mg/L] that decreased significantly to 2.4 (IQR: 1.4-3.9) mg/L after 40 days after symptom onset (p<0.0001). Performance of CRP levels determined using ROC analysis distinguished severe from non-severe COVID-19 patients, with an AUC value of 0.83 (95% CI: 0.73-0.91; p=0.001; 77.4% sensitivity and 89.4% specificity). In multivariable analysis, CRP levels above 30 mg/L were significantly associated with an increased risk of developing severe COVID-19 for those who have higher ages and comorbidities (ARR 3.99, 95% CI: 1.35-11.82; p=0.013). CRP was found to be an independent determinant factor for severe COVID-19 patients. Therefore, CRP levels in COVID-19 patients in African settings may provide a simple, prompt, and inexpensive assessment of the severity status at baseline and monitoring of treatment outcomes.

Chronic immune activation has been considered as the driving force for CD4+ T cell depletion in people infected with HIV-1. Interestingly, the normal immune profile of adult HIV-negative individuals living in Africa also exhibit chronic immune activation, reminiscent of that observed in HIV-1 infected individuals. It is characterized by increased levels of soluble immune activation markers, such as the cytokines interleukin (IL)-4, IL-10, TNF-α, and cellular activation markers including HLA-DR, CD-38, CCR5, coupled with reduced naïve and increased memory cells in CD4+ and CD8+ subsets. In addition, it is accompanied by low CD4+ T cell counts when compared to Europeans. There is also evidence that mononuclear cells from African infants secrete less innate cytokines than South and North Americans and Europeans in vitro. Chronic immune activation in Africans is linked to environmental factors such as parasitic infections and could be responsible for previously observed immune hypo-responsiveness to infections and vaccines. It is unclear whether the immunogenicity and effectiveness of anti-SARS-CoV-2 vaccines will also be reduced by similar mechanisms. A review of studies investigating this phenomenon is urgently required as they should inform the design and delivery for vaccines to be used in African populations.