Informing a target product profile for rapid tests to identify HBV-infected pregnant women with high viral loads: a discrete choice experiment with African healthcare workers.

BACKGROUND: Elimination of mother-to-child transmission of hepatitis B virus (HBV) requires infant immunoprophylaxis and antiviral prophylaxis for pregnant women with high viral loads. Since real-time polymerase chain reaction (RT-PCR), a gold standard for assessing antiviral eligibility, is neither accessible nor affordable for women living in low-income and middle-income countries (LMICs), rapid diagnostic tests (RDTs) detecting alternative HBV markers may be needed. To inform future development of the target product profile (TPP) for RDTs to identify highly viremic women, we used a discrete choice experiment (DCE) and elicited preference and trade-off of healthcare workers (HCW) in Africa between the following four attributes of fictional RDTs: price, time-to-result, diagnostic sensitivity, and specificity. METHODS: Through an online questionnaire survey, we asked participants to indicate their preferred test from a set of two RDTs in seven choice tasks with varying levels of the four attributes. We used mixed multinomial logit models to quantify the utility gain or loss generated by each attribute. We attempted to define minimal and optimal criteria for test attributes that can satisfy ≥ 70% and ≥ 90% of HCWs, respectively, as an alternative to RT-PCR. RESULTS: A total of 555 HCWs from 41 African countries participated. Increases in sensitivity and specificity generated significant utility and increases in cost and time-to-result generated significant disutility. The size of the coefficients for the highest attribute levels relative to the reference levels were in the following order: sensitivity (ß = 3.749), cost (ß = -2.550), specificity (ß = 1.134), and time-to-result (ß = -0.284). Doctors cared most about test sensitivity, while public health practitioners cared about cost and midwives about time-to-result. For an RDT with 95% specificity, costing 1 US$, and yielding results in 20 min, the minimally acceptable test sensitivity would be 82.5% and the optimally acceptable sensitivity would be 87.5%. CONCLUSIONS: African HCWs would prefer an RDT with the following order of priority: higher sensitivity, lower cost, higher specificity, and shorter time-to-result. The development and optimization of RDTs that can meet the criteria are urgently needed to scale up the prevention of HBV mother-to-child transmission in LMICs.

Pseudomyxoma peritonei induced by a well-differentiated appendicular mucinous adenocarcinoma: An uncommon cause of isolated ascites in a young man patient.

Pseudomyxoma peritonei (PMP) remains difficult to diagnose and has a reserved prognosis. Pseudomyxoma peritonei is a rare entity, of appendicular origin in the majority of cases. Its clinical symptomatology is not specific, and the diagnosis is evoked by imaging and surgery and confirmed by histology.

Factors Associated with in-Hospital Mortality in Malagasy Patients with Acute Decompensation of Liver Cirrhosis: A Retrospective Cohort.

Background: Cirrhosis is a pathology responsible for a significant hospital morbidity and mortality. The objective of this study was to determine the factors associated with hospital mortality in a sample of Malagasy cirrhotics. Patients and Methods: This was a retrospective cohort study from January 2018 to August 2020 conducted in the Hepato-Gastroenterology Unity, University Hospital Joseph Raseta Befelatanana, Antananarivo, Madagascar. Results: One hundred and eight patients were included. The mean age was 51.13±13.50 years with a sex ratio of 2.37. The etiology of cirrhosis was dominated by alcohol (44.44%), hepatitis B virus (24.07%) and hepatitis C virus (13.89%). Twenty-eight patients (25.93%) had died. Factors associated with in-hospital mortality were hepatic encephalopathy (OR: 14.16; 95% CI: 5.08-39.4; p: 0.000), renal failure (OR: 8.55; 95% CI: 2.03-39.9; p: 0.0034), gastrointestinal bleeding (OR: 3.25; 95% CI: 1.32-7.92; p: 0.0099), hyponatraemia <130mmol/L (OR: 3.34; 95% CI: 1.04-10.6; p=0.046), Child-Pugh C classification (OR: 0.19; 95% CI: 0.12-0.21; p: 0.000), and MELD-Na score >32 (OR: 27.5; 95% CI: 4.32-174.8; p: 0.004). Conclusion: The in-hospital mortality rate during acute decompensation of cirrhosis remains high in Madagascar. Hepatic encephalopathy, renal failure, GI bleeding and hyponatraemia are the main clinico-biological factors affecting in-hospital mortality. Early intervention on these modifiable factors is an important step to improve hospital outcomes. The natraemia, MELD score and MELD-Na score should be used in routine practice in Madagascar to identify patients with acute decompensation of cirrhosis at high risk of death.

Gastrointestinal Mucormycosis-Induced Massive Lower Gastrointestinal Bleeding, Rectal Perforation, and Pulmonary Embolism: A Long Diagnostic Pathway in a Case Report.

Introduction: Mucormycosis is a rare systemic fungal infection, mainly observed in immunocompromised patients. It is responsible for surface and deep tissue destruction leading to perforations and hemorrhage. Its pathogenesis represented by an angio-invasion is at the origin of a local infarction and a vascular thrombosis. We report a case of gastrointestinal (GI) mucormycosis-induced multiple gastric ulcers, GI bleeding and rectal perforation. Case Presentation: A 75-year-old man, with type II diabetes mellitus, was admitted to the intensive care unit for an acute abdominal pain associated with massive hematochezia. Clinical examination was that of an acute peritonitis and a hemorrhagic shock state. Abdominal and pelvic CT scan with intravenous contrast concluded to a perforation of the anterior wall of the rectum. He underwent immediate laparotomy with temporary colostomy. Several upper GI endoscopies had shown multiple gastric ulcer lesions. Lower GI endoscopy showed a fistulous orifice of the rectum on its anterior surface. Histopathology of the gastric biopsy showed acute and subacute inflammatory changes with filamentous elements suggesting mucormycosis. Histopathology of the rectal biopsy showed a subacute non-specific inflammation. Culture of the secretions from the rectal fistula orifice showed the strain Rhizopus sp. Antifungal susceptibility testing reported sensitivity to liposomal amphotericin B. The diagnosis of GI mucormycosis-induced multiple gastric ulcers, rectal perforation and pulmonary embolism in the patient with type II diabetes mellitus was retained. The outcomes were favorable after 6 weeks of treatment with liposomal amphotericin B associated with temporary colostomy and appropriate diabetes management. Conclusion: GI mucormycosis remains a multidisciplinary diagnostic challenge, less frequent in clinical practice, with a long diagnostic pathway. This opportunistic systemic mycosis can lead to numerous GI complications including perforation, massive GI bleeding and even multiple extra-GI complications. GI mucormycosis has a good prognosis if it is treated early with medical and surgical treatment.

Effectiveness and Safety of Low Dose of Tenofovir Disoproxil Fumarate in Malagasy Patients with Chronic Hepatitis B.

Background: Accessibility of full dose daily of tenofovir disoproxil fumarate (TDF) is limited in Madagascar with an estimated cost well above the purchasing power of Malagasy population. Objective: The study is aimed at evaluating the efficacy and safety of low-dose tenofovir for the treatment of chronic hepatitis B (CHB). Methods: This prospective cohort study from January 2018 to December 2020 was conducted in the Department of Hepato-Gastroenterology, University Hospital Joseph Raseta Befelatanana, Antananarivo, Madagascar. The patients enrolled in the study received low dose of TDF 900 mg/week (300 mg daily, three days per week). Results: A total of 45 patients (male/female: 31/14) were included. The mean age was 45.1 ± 11.5 years. Fifteen patients were nucleos(t)ide (NA)-naïve, and 30 patients had prior NA therapy (NA-experienced). Thirty patients were HBeAg positive. A complete virological response (CVR) was achieved in 36/45 patients (80%) at 3 months, 41/45 (91.1%) at 6 months, and 43/45 (95.6%) at 12 months. High viral load at baseline was negative predictive factor of CVR at 3 months (HR: 0.14; 95% CI: 0.022-0.92; p: 0.041). There was no significant difference in response between HBeAg-positive and HBeAg-negative patients, NA-naïve and NA-experienced patients, and cirrhotic and noncirrhotic patients. Low dose of tenofovir was well tolerated. Ten patients (22.22%) had mild side effects. Mild renal failure was observed in 3 patients (6.7%) during follow-up. Conclusion: Low dose of tenofovir is effective, safe, and well tolerated in a Malagasy population sample. These results still require verification in a large population.

Splenectomy Combined with Endoscopic Variceal Ligation (EVL) versus EVL Alone for Secondary Prophylaxis of Variceal Bleeding in Hepatosplenic Schistosomiasis: A Retrospective Case-Control Study.

Background: Hepatosplenic schistosomiasis (HSS) is one of the most common causes of portal hypertension in developing countries. Variceal bleeding is the most common cause of mortality during HSS. The objective of this study was to evaluate the efficacy of splenectomy associated with endoscopic variceal ligation (EVL) compared with EVL alone in preventing variceal bleeding in patients with HSS. Methods: This was a single-center, retrospective, case-control study. Between January 2015 and December 2019, a total of 59 patients with HSS who had at least one variceal bleeding episode and received EVL with or without splenectomy were identified and stratified. In this case-control design, 22 patients had splenectomy + EVL (case group) and 37 patients had EVL alone (control group). The main endpoints were the rate of variceal rebleeding and the mortality rate between the two groups. Results: The mean age of our patients was 39.92 ± 13.4 (19-75) years with a sex ratio of 1.8. The recurrence rate of variceal bleeding was significantly lower in the case group (splenectomy + EVL) than in the control group (EVL alone) (4.45% vs 27.2%, p = 0.041). There was no significant difference between the two groups in terms of mortality (4.54 vs 2.7%, p = 1.00). Conclusion: Splenectomy combined with EVL was effective than EVL alone in preventing variceal rebleeding in patients with HSS.

COVID-19 Induced Acute Pancreatitis in a Malagasy Woman Patient: Case Report and Literature Review.

Background: SARS-CoV-2 has been described as a respiratory tropic virus since its emergence in December 2019. During the course of the disease, other extra-pulmonary manifestations have been reported in the literature including pancreatic involvement such as acute pancreatitis. This phenomenon linking COVID-19 and acute pancreatitis has been reported by several case reports and cohort studies. No cases had been reported in sub-Saharan Africa and Madagascar. We report one more case Of COVID-19 induced acute pancreatitis in a Malagasy woman patient without risk factors, further consolidating the existing evidence. Case Presentation: A 44-year-old woman was diagnosed with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and had a favorable course under home isolation and drug treatments. One week later, the patient was admitted to hospital with severe acute abdominal pain. Acute pancreatitis was considered according to the revised Atlanta criteria with the presence of the three criteria. Other etiologies of acute pancreatitis (lithiasis, alcohol, hypercalcemia, hypertriglyceridemia, tumor, trauma, surgery) were excluded. Ultimately, a COVID-19 induced acute pancreatitis was retained. The outcome was favorable under symptomatic medical treatment (fluid resuscitation, bowel rest, management of pain and vomiting, and early oral feeding). The patient was discharged after one week of hospitalization. Conclusion: COVID-19 is a possible etiology of acute pancreatitis. Acute pancreatitis should be routinely ruled out in a patient with COVID-19 infection with acute abdominal pain.

Carvedilol versus propranolol in the prevention of variceal rebleeding in hepatosplenic schistosomiasis: Efficacy and safety.

Background and Aim: Beta blockers combined with endoscopic variceal band ligation (EVL) is the most effective means for the prevention of variceal rebleeding. No data are available on the efficacy of carvedilol in the secondary prophylaxis of variceal bleeding in hepatosplenic schistosomiasis. The aim of this study was to evaluate the efficacy and safety of carvedilol compared to propranolol as secondary prophylaxis of variceal bleeding in hepatosplenic schistosomiasis. Methods: This was a prospective, randomized study over a period of 14 months from February 2019 to March 2020. All patients with portal hypertension due to schistosomiasis with at least one episode of variceal bleeding were included and randomized to the propranolol and carvedilol groups. EVL protocol was continued in both groups. Results: Sixty-one patients were eligible and randomized to propranolol (n = 30) and carvedilol (n = 31) groups. There was no significant difference in hemorrhagic recurrence between the carvedilol (n = 1) and propranolol (n = 3) groups (3.33 vs 10%; P = 0.30). At 4 months, there was a significant reduction in mean arterial pressure (-4.13 mm Hg; 95% CI: -6.27 to -1.99; P < 0.05) and heart rate (-12.13 bpm; 95% CI: -13.92 to -10.35; P < 0.05) in the carvedilol group. There was no significant difference between the groups on the mean difference in arterial pressure. One patient in the carvedilol group had breathing difficulty. There were no adverse events in the propranolol group. Conclusion: There was no significant difference in the efficacy between carvedilol and propranolol. Carvedilol may be an alternative to propranolol for secondary prophylaxis of variceal rebleeding in hepatosplenic schistosomiasis.

Demographic, clinical and aetiological characteristics of patients with hepatocellular carcinoma followed between 2012 and 2017 at University Hospital Joseph Raseta Befelatanana, Antananarivo, Madagascar.

Purpose: The aim of this study was to describe the demographic, clinical and aetiological characteristics of hepatocellular carcinoma (HCC) in a Malagasy population sample in view to defining an appropriate control program. Methods: This was a retrospective, descriptive study conducted in the Gastroenterology Department, Joseph Raseta Befelatanana University Hospital, Antananarivo, over a period of 6 years (January 2012 to December 2017). Results: A total of 42 patients were selected, 29 of whom were men (69.05%) and 13 women (30.95%) (sex ratio: 2.2). The mean age was 56.6 years with extremes of 21 and 82 years. Subjects aged 60-69 years were most affected (35.71%). Abdominal pain was the main revealing symptom (38.10%). The main aetiological factors were: hepatitis B virus (HBV) (42.86%), hepatitis C virus (19.05%) and chronic alcoholism (23.81%). All patients were cirrhotic, of which 23 patients (54.76%) had Child-Pugh B class and 15 (35.71%) Child-Pugh C. Twenty-six patients (61.90%) had α-foetoprotein level plus 500 ng/mL. Six patients (14.29%) had portal thrombosis at diagnosis. Twenty patients (47.62%) had advanced HCC (Barcelona Clinic Liver Cancer C (BCLC C)) and 21 (50%) had end-stage HCC (BCLC D). Management was palliative in 41/42 patients. The in-hospital death rate was 23.81%. Conclusion: HCC are diagnosed at advanced stage in this study. The prognosis is poor for most patients. HBV infection is the main risk factor. An effort should be made for early diagnosis and prevention.

Arteria lusoria: A rare cause of chronic dysphagia.

Arteria lusoria is a rare cause of dysphagia in which dysphagia due to esophageal compression. The upper GI endoscopy does not bring significant element that can orient the diagnosis. The injected thoracic CT scan remains the key examination for the diagnosis of dysphagia lusoria and to characterize the defective artery.

Acute infectious pancreatitis due to Salmonella typhi: Case report and literature review.

Salmonella typhi remains an endemic disease in Madagascar. Acute pancreatitis remains a rare complication of S. typhi colitis. We presented the case of a 27-year-old male, admitted to febrile diarrhea, vomiting, and severe abdominal pain. Blood work-up revealed elevated plasma lipase level. Abdominal CT scan showed acute pancreatitis without necrosis. Blood and stool culture positivity for S. typhi. Patient was diagnosed as acute pancreatitis caused by S. typhi. The outcome was favorable under symptomatic medical treatment (rehydration and analgesic) combined with adapted antibiotic therapy. Acute pancreatitis is a possible complication of Salmonella infections. The presence of severe abdominal pain and febrile diarrhea should draw clinicians' attention to possible Salmonella acute pancreatitis.

Inappropriate prescription of corticosteroid therapy during inflammatory ileo-colitis revealing disseminated tuberculosis with digestive involvement: Two case reports.

It is essential to differentiate intestinal tuberculosis from Crohn's disease because of the therapeutic implications of Crohn's disease, which can exacerbate the symptoms of tuberculosis.

Treatment of viral hepatitis C genotypes 1 and 2 by sofosbuvir and ledipasvir with or without ribavirin combination: A possible alternative to pangenotypic treatment in a low-income country?

OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of sofosbuvir/ledipasvir ± ribavirin in Malagasy patients with hepatitis C virus genotypes 1 and 2, in real conditions. PATIENTS AND METHODS: This was a retrospective monocentric clinical study, carried out over a period of 3 years from March 1, 2017 to February 28, 2020, in a hospital hepato-gastroenterology department. RESULTS: In total, 26 patients (M/F: 11/15) with hepatitis C virus genotype 1 (n = 13) or genotype 2 (n = 13), were treated with sofosbuvir/ledipasvir without (n = 21) or with (n = 5) ribavirin for 12 weeks. The mean age was 61.38 ± 7.09 years. Seventeen patients (65.4%) had cirrhosis. The overall sustained virological response was 96.2% (95% CI = 80.4-99.9%). There was no significant difference between the sustained virological responses of genotypes 1 and 2 (92.3% vs 100%; p = 0.31) or those of cirrhotic or non-cirrhotic patients (94.1% vs 100%; p = 0.46). A relapse was observed in one patient (5.9%) - cirrhotic and genotype 1b - under sofosbuvir/ledipasvir with ribavirin. Seven patients (26.9%) experienced mild adverse reactions, including asthenia (57.1%) and insomnia (42.9%). CONCLUSION: Treatment with sofosbuvir/ledipasvir ± ribavirin for infection with hepatitis C virus genotype 1 has been shown to be safe and effective, even in the presence of cirrhosis. The sofosbuvir/ledipasvir combination is a good option for genotype 2 non-cirrhotic patients.

Primary biliary cholangitis-autoimmune hepatitis overlap syndrome: Case report and literature review.

Paris criteria remain practical for retaining the diagnosis of overlap syndrome. While liver histology is mandatory, its absence should not be an obstacle to the diagnosis and delay the initiation of treatment in countries where biopsy not available.

Clinical mortality risk factors of variceal upper gastrointestinal bleeding in a Malagasy surgical intensive care unit.

BACKGROUND: Variceal upper gastrointestinal bleeding is a dreadful complication of portal hypertension with a significant morbidity and mortality. Different prognostic scores can be used. However, in the local context of Madagascar, the completion of paraclinical investigations can be delayed by the limited financial means of patients. Hence, determining clinical mortality risk factors of variceal upper gastrointestinal bleeding could be interesting. The aim of the study was to evaluate the clinical mortality risk factors of variceal gastrointestinal bleeding (VUGIB). METHOD: An observational, cohort retrospective study was conducted over an 8-year period (2010-2017), at the surgical intensive care unit of the J.R. Andrianavalona University Hospital, Antananarivo, in patients admitted for VUGIB confirmed by upper gastrointestinal endoscopy and whose clinical examination was performed at admission. The primary endpoint was intensive care unit (ICU) mortality. Univariate analysis and multivariate logistic regression analysis were performed to identify risk factors for ICU mortality, with OR defining odds ratio. A p value <0.05 was considered significant. RESULTS: 1920 patients were admitted for gastrointestinal bleeding of any digestive causes; the source of bleeding was variceal in 269 patients (14%). The predominantly male population (sex ratio = 2.5), aged 47.1 ± 13.7 years was mostly American Society of Anesthesiologists (ASA) 1 classification (58.4%). In 56.5% of patients, the gastrointestinal bleeding had not occurred before. The mortality rate was 16.0%. Three major clinical factors of mortality were identified: previous endoscopic band variceal ligation (OR = 12.57 [2.18-72.58], p = 0.005), tachycardia >120 bpm (OR = 2.91 [1.04-8.14], p = 0.041), and ascites (OR = 3.80 [1.85-7.81], p < 0.001). CONCLUSION: Upper gastrointestinal bleeding may be life-threatening. The mortality scores are certainly useful; however, the identification of clinical factors is interesting in countries like Madagascar, pending the results of paraclinical investigations.

A case of synchronous association of a jejunal stromal tumor and a colic adenocarcinoma.

Gastrointestinal stromal tumors are the most common mesenchymal tumors of the gastrointestinal tract. They are generally considered as solitary tumors. Here we report the case of a 66-year-old man with familial history of digestive cancers, admitted after a 2-months history of gastrointestinal bleeding. Colonoscopy showed a circumferential ulcerated tumor of the sigmoid which was a well differentiated adenocarcinoma on biopsy. Computerized tomography showed only the lesion of the sigmoid. The patient underwent a left colectomy followed by immediate end-to-end anastomosis. Per-operatively, jejunal mass was discovered and a jejunal segmentectomy was performed. Pathologic examination revealed a colic adenocarcinoma pT2N0M0 associated with a low risk stromal tumor of the jejunum CD117+ and DOG-1+. No adjuvant therapy was given. After 64 months of follow-up, the patient showed no evidence of recurrence. Clinicians should be aware of the coexistence of malignancies and carry careful investigations for accurate diagnosis and better patients' prognosis.

Population genetic structure and isolation by distance of Helicobacter pylori in Senegal and Madagascar.

Helicobacter pylori has probably infected the human stomach since our origins and subsequently diversified in parallel with their human hosts. The genetic population history of H. pylori can therefore be used as a marker for human migration. We analysed seven housekeeping gene sequences of H. pylori strains isolated from 78 Senegalese and 24 Malagasy patients and compared them with the sequences of strains from other geographical locations. H. pylori from Senegal and Madagascar can be placed in the previously described HpAfrica1 genetic population, subpopulations hspWAfrica and hspSAfrica, respectively. These 2 subpopulations correspond to the distribution of Niger-Congo speakers in West and most of subequatorial Africa (due to Bantu migrations), respectively. H. pylori appears as a single population in Senegal, indicating a long common history between ethnicities as well as frequent local admixtures. The lack of differentiation between these isolates and an increasing genetic differentiation with geographical distance between sampling locations in Africa was evidence for genetic isolation by distance. The Austronesian expansion that started from Taiwan 5000 years ago dispersed one of the 10 subgroups of the Austronesian language family via insular Southeast Asia into the Pacific and Madagascar, and hspMaori is a marker for the entire Austronesian expansion. Strain competition and replacement of hspMaori by hpAfrica1 strains from Bantu migrants are the probable reasons for the presence of hspSAfrica strains in Malagasy of Southeast Asian descent. hpAfrica1 strains appear to be generalist strains that have the necessary genetic diversity to efficiently colonise a wide host spectrum.