Methotrexate-induced toxidermia and pancytopenia in a patient with ectopic pregnancy: a case report

Background Methotrexate is an anticancer drug from the antimetabolite class. It is also used in gynecology and obstetrics and is the molecule of choice for the medical treatment of ectopic pregnancies. We report a case of toxidermia associated with severe pancytopenia induced by methotrexate for ectopic pregnancy. Case presentation A 30-year-old Malagasy (African) woman was admitted to the Emergency and Intensive Care Department for probable toxidermia following injection of 75 mg of methotrexate for an ectopic pregnancy. She had developed generalized erythema, which started 48 hours after the injection. The secondary onset of phlyctenular maculopapular skin lesions, generalized purpura, and erosions of the oral mucosa in a context of febrile jaundice prompted her hospitalization. On admission, the patient presented with febrile neutropenia, pancytopenia, renal failure, and hepatic cytolysis. She received transfusions of fresh whole blood, erythromycin, and amphotericin B. The course was fatal within 2 days of hospitalization. The patient died of multiple organ failure. Conclusions Our case is mainly distinguished by the lack of use of granulocyte growth factors and folinic acid. In the event of severe reactions to methotrexate, the management should be multidisciplinary and as much as possible within an intensive care unit.

Prevalence and Diversity of Hepatitis Virus Markers among Patients with Acute Febrile Jaundice in Chad

Only a minority of the patients with acute febrile jaundice evaluated through the Yellow Fever surveillance program were found positive for antibodies against Yellow Fever Virus (YFV). In order to characterize patients with acute febrile jaundice negative for YFV, we collected 255 sera between January to December 2019. We screened for HBV antigens, and antibodies against HCV and HEV. The seroprevalences observed were 10.6% (27/255) for HBV, 2% (5/255) for HCV, 17.3% (44/255) for HEV IgG, 4.3% (11/255) for HEV IgM, and 12.5% (32/255) for both IgG and IgM HEV. Prevalence of HEV was significantly higher in females than males (p < 0.01). HEV IgG prevalence was highest in those 20–29 years old, but the highest incidence rate (IgM positive) was in children 0–9 years old. Exposure to HEV was higher in the Sahelian zone (55.8%, 95% CI: 40.97–70.66) than in the Sudanese zone (30.2%, 95% CI: 24.01–36.37, p = 0.003). The high prevalence rates and hepatitis virus diversity underline the challenge of routine clinical diagnosis in Chad’s Yellow Fever surveillance program.

Viral Causes of Acute Febrile Jaundice in Selected Provinces of Zambia

Background Following the yellow fever (YF) risk assessment conducted in 2013, Ministry of Health in collaboration with WHO successfully implemented YF case based surveillance among the YF suspects in the high risk areas of Zambia. To date, none of the patients has been confirmed as a case of YF and the epidemiology of flavi-viruses has not been comprehensively investigated in Zambia. As YF may be hardly distinguished clinically from other febrile diseases, because early in the clinical course YF may appear similar to other diseases but YF will diverge clinically as the disease course progresses. This study was designed to investigate the viral causes of febrile jaundice among YF suspects in selected provinces of Zambia. Method We conducted a retrospective study on 93 archived serum samples previously collected from patients meeting a case definition of YF suspect from January 2014 to July 2015 presented in selected health facilities. Yellow Fever, Dengue Fever, West Nile, pan Flavivirus, and Hepatitis A viruses were tested by reverse transcriptase polymerase chain reaction (RT_PCR) and Hepatitis B virus using PCR, while Hepatitis C and Hepatitis E viruses were tested by nested polymerase chain reaction (nPCR). Samples were also tested for YF and dengue fever (DF) antibodies using in-house immunoglobulin M enzyme linked immunosorbent assay (Ig M ELISA) and immunoglobulin M rapid test respectively. STATA version 12 was used for data analysis. Results Fourteen percent (13/93) of the serum samples were identified as YF IgM positive. None of the samples tested positive for DF IgM ELISA. All 93 serum samples tested negative for the flaviviruses by RT-PCR. However, 8.6% (8/93) showed acute Hepatitis A and 2/20 (10%) of pooled sera tested positive for HBV. The median age of patients with Hepatitis A was 9.5 years old and for those without evidence of HAV infection was 19 years old. Approximately 85 (91.4%) of patients had acute diseases of unknown origin. Conclusion The study revealed that YF IgM was prevalent among study participants. However, the causes of fever and jaundice in Zambia may include viral hepatitis and needs to be considered if flaviviral diseases are suspected.

Herpes Infections in Suspected Cases of Yellow Fever in the Democratic Republic of the Congo

In the battle to quickly identify potential yellow fever arbovirus outbreaks in the Democratic Republic of the Congo, active syndromic surveillance of acute febrile jaundice patients across the country is a powerful tool. However, patients who test negative for yellow fever virus infection are too often left without a diagnosis. By retroactively screening samples for other potential viral infections, we can both try to find sources of patient disease and gain information on how commonly they may occur and co-occur. Several human arboviruses have previously been identified, but there remain many other viral families that could be responsible for acute febrile jaundice. Here, we assessed the prevalence of human herpes viruses (HHVs) in these acute febrile jaundice disease samples. Total viral DNA was extracted from serum of 451 patients with acute febrile jaundice. We used real-time quantitative PCR to test all specimens for cytomegalovirus (CMV), herpes simplex virus (HSV), human herpes virus type 6 (HHV-6) and varicella-zoster virus (VZV). We found 21.3% had active HHV replication (13.1%, 2.4%, 6.2% and 2.4% were positive for CMV, HSV, HHV-6 and VZV, respectively), and that nearly half (45.8%) of these infections were characterized by co-infection either among HHVs or between HHVs and other viral infection, sometimes associated with acute febrile jaundice previously identified. Our results show that the role of HHV primary infection or reactivation in contributing to acute febrile jaundice disease identified through the yellow fever surveillance program should be routinely considered in diagnosing these patients.

Herpes Infections in Suspected Cases of Yellow Fever in the Democratic Republic of the Congo

In the battle to quickly identify potential yellow fever arbovirus outbreaks in the Democratic Republic of the Congo, active surveillance of acute febrile jaundice patients across the country is a powerful tool. However, patients who test negative for yellow fever virus infection are too often left without a diagnosis. By retroactively screening samples for other potential viral infections, we can both try to find sources of patient disease and also gain information on how commonly they circulate in the population. Here, we assessed the prevalence of human herpes viruses (HHVs) in these acute febrile jaundice disease samples. We found 22.6% had active HHV replication, and that over half were characterized by co-infection either among HHVs or between HHVs and other viral infections previously identified. Our results show that the role of HHV primary infection or reactivation in contributing to acute febrile jaundice disease should be further investigated.

High Prevalence and Diversity of Hepatitis Viruses in Suspected Cases of Yellow Fever in the Democratic Republic of Congo

ABSTRACTThe majority of patients with acute febrile jaundice (>95%) identified through a yellow fever surveillance program in the Democratic Republic of Congo (DRC) test negative for antibodies against yellow fever virus. However, no etiological investigation has ever been carried out on these patients. Here, we tested for hepatitis A (HAV), hepatitis B (HBV), hepatitis C (HCV), hepatitis D (HDV), and hepatitis E (HEV) viruses, all of which can cause acute febrile jaundice, in patients included in the yellow fever surveillance program in the DRC. On a total of 498 serum samples collected from suspected cases of yellow fever from January 2003 to January 2012, enzyme-linked immunosorbent assay (ELISA) techniques were used to screen for antibodies against HAV (IgM) and HEV (IgM) and for antigens and antibodies against HBV (HBsAg and anti-hepatitis B core protein [HBc] IgM, respectively), HCV, and HDV. Viral loads and genotypes were determined for HBV and HVD. Viral hepatitis serological markers were diagnosed in 218 (43.7%) patients. The seroprevalences were 16.7% for HAV, 24.6% for HBV, 2.3% for HCV, and 10.4% for HEV, and 26.1% of HBV-positive patients were also infected with HDV. Median viral loads were 4.19 × 105IU/ml for HBV (range, 769 to 9.82 × 109IU/ml) and 1.4 × 106IU/ml for HDV (range, 3.1 × 102to 2.9 × 108IU/ml). Genotypes A, E, and D of HBV and genotype 1 of HDV were detected. These high hepatitis prevalence rates highlight the necessity to include screening for hepatitis viruses in the yellow fever surveillance program in the DRC.

The Pitfalls of Febrile Jaundice. A Case Report

Jaundice in sepsis is usually caused by cholestasis, and its onset can precede other manifestations of the infection. Inflammation-induced cholestasis is a common complication in patients with an extrahepatic infection or those with inflammatory processes. We describe the case of a 47 years old female who presented with low back pain and paravertebral muscular contracture. She subsequently developed a cholestatic syndrome with clinical manifestations such as jaundice, followed by fever and sepsis with multiple organ dysfunction. Initially labeled as biliary sepsis, the diagnosis was crucially reoriented as the blood cultures were positive for Streptococcus pyogenes and the magnetic resonance imaging (MRI) findings suggested spondylodiscitis as well as a paravertebral abscess.