Diagnosis of neglected tropical diseases among patients with persistent digestive disorders (diarrhoea and/or abdominal pain ≥14 days): Pierrea multi-country, prospective, non-experimental case-control study.

BACKGROUND: Diarrhoea still accounts for considerable mortality and morbidity worldwide. The highest burden is concentrated in tropical areas where populations lack access to clean water, adequate sanitation and hygiene. In contrast to acute diarrhoea (<14 days), the spectrum of pathogens that may give rise to persistent diarrhoea (≥14 days) and persistent abdominal pain is poorly understood. It is conceivable that pathogens causing neglected tropical diseases play a major role, but few studies investigated this issue. Clinical management and diagnostic work-up of persistent digestive disorders in the tropics therefore remain inadequate. Hence, important aspects regarding the pathogenesis, epidemiology, clinical symptomatology and treatment options for patients presenting with persistent diarrhoea and persistent abdominal pain should be investigated in multi-centric clinical studies. METHODS/DESIGN: This multi-country, prospective, non-experimental case-control study will assess persistent diarrhoea (≥14 days; in individuals aged ≥1 year) and persistent abdominal pain (≥14 days; in children/adolescents aged 1-18 years) in up to 2000 symptomatic patients and 2000 matched controls. Subjects from Côte d'Ivoire, Indonesia, Mali and Nepal will be clinically examined and interviewed using a detailed case report form. Additionally, each participant will provide a stool sample that will be examined using a suite of diagnostic methods (i.e., microscopic techniques, rapid diagnostic tests, stool culture and polymerase chain reaction) for the presence of bacterial and parasitic pathogens. Treatment will be offered to all infected participants and the clinical treatment response will be recorded. Data obtained will be utilised to develop patient-centred clinical algorithms that will be validated in primary health care centres in the four study countries in subsequent studies. DISCUSSION: Our research will deepen the understanding of the importance of persistent diarrhoea and related digestive disorders in the tropics. A diversity of intestinal pathogens will be assessed for potential associations with persistent diarrhoea and persistent abdominal pain. Different diagnostic methods will be compared, clinical symptoms investigated and diagnosis-treatment algorithms developed for validation in selected primary health care centres. The findings from this study will improve differential diagnosis and evidence-based clinical management of digestive syndromes in the tropics. TRIAL REGISTRATION: ClinicalTrials.gov; identifier: NCT02105714 .

Efficacy and safety of convalescent plasma therapy in patients with moderate-to-severe COVID-19: A non-randomized comparative study with historical control in a referral hospital in Indonesia.

BACKGROUND: Studies to confirm the efficacy and safety of convalescent plasma (CP) as an adjunctive treatment for COVID-19 are still required especially for the countries where standard treatments are unevenly distributed. METHODS: A non-randomized comparative study was done from June - September 2020 in Dr. Sardjito Hospital, Yogyakarta, Indonesia. Plasma with anti-SARS-CoV-2 specific IgG titer of >1:320 were used. Primary end points were clinical and laboratory parameters outcome including BGA, chest X-ray, CT value, CRP, procalcitonin, IL-6, D-Dimer and ALC examined on day 1, 2 and 7 post-transfusion. RESULTS: The experimental arm of this study consisted of 15 patients who received CP: 3 (20%) with moderate COVID-19 and 12 (80%) with severe COVID-19. There were 15 historical controls in this study. Ten recipients survived and 5 deceased (survival rate was 66.7%). There were higher rate of pneumonia resolution (OR 1.54, CI95% 0.33-7.23), ARDS resolution (OR 1.20, CI95% 0.25-5.84) and shorter median length of stay (20 vs 22 days, p = 0.41) among recipients compared to controls. Lower mortality rate was observed in recipients vs controls (33.3% vs 46.7% (OR 0.75, CI95% 0.17-3.33)). Median death onset was longer in recipient vs control (7th vs 1st day, p = 0.13). Survival analysis showed protective effect of CP (HR 0.69, CI 95% 0.21-2.27, p = 0.545). Higher CT value improvement (p = 0.51) and negative conversion rate (OR1.20, CI95% 0.25-5.84) were observed in recipients compared to controls. Sub-analysis showed more number of comorbidities, higher procalcitonin and higher D-Dimer among CP recipients who did not survive (p = 0.02 and p = 0.02 respectively). Lower CRP and procalcitonin, and higher ALC were found in survivors compared to non-survivors (p = 0.0437; p = 0.0049; and p = 0.0002 respectively). CONCLUSION: This study showed promising results for CP marked by improvements in clinical outcome, as well as significant reduction of inflammatory markers among recipients.