ro13-9904 and Malaria

Nontyphoidal Salmonella (NTS), mainly serotypes Typhimurium and Enteritidis, cause invasive infections with high mortality in children in sub-Saharan Africa. Multidrug resistance is common, and resistance to third-generation cephalosporins has emerged.. We reviewed clinical features, outcomes, and antimicrobial resistance patterns in invasive NTS infections among children aged 6 weeks to 5 years participating in malaria vaccine studies in an area of high malaria and human immunodeficiency virus (HIV) transmission in Siaya, western Kenya. Blood culture was performed in hospitalized children and pediatric outpatients with prolonged fever.. From July 2009 to December 2013, 1696 children aged 6 weeks to 17 months were enrolled into vaccine trials and followed for up to 53 months. We obtained 1692 blood cultures from 847 children. Of 134 bacterial pathogens isolated, 102 (76.1%) were Salmonella serogroup B or D. Invasive NTS disease occurred in 94 (5.5%) children, with an incidence of 1870, 4134, and 6510 episodes per 100 000 person-years overall, in infants, and in HIV-infected children, respectively. Malaria infection within the past 2 weeks occurred in 18.8% (3/16) of invasive NTS episodes in HIV-infected and 66.2% (53/80) in HIV-uninfected children. Case fatality rate was 3.1%. Salmonella group B resistant to ceftriaxone emerged in 2009 and 2010 (6.2% [2/32 isolates]), rising to 56.5% (13/23 isolates) in 2012 and 2013.. Incidence of invasive NTS disease was high in this area of high malaria and HIV transmission, especially in HIV-infected children. Rapidly emerging resistance against ceftriaxone requires urgent reevaluation of antibiotic recommendations and primary prevention of exposure to Salmonella.

Topics: Anti-Bacterial Agents; Bacteremia; Ceftriaxone; Child, Preschool; Drug Resistance, Multiple, Bacterial; Female; HIV Infections; Hospitalization; Humans; Incidence; Infant; Kenya; Malaria; Male; Outpatients; Residence Characteristics; Rural Population; Salmonella enterica; Salmonella Infections; Time Factors

Tropical infections form 20-30% of ICU admissions in tropical countries. Diarrheal diseases, malaria, dengue, typhoid, rickettsial diseases and leptospirosis are common causes of critical illness. Overlapping clinical features makes initial diagnosis challenging. A systematic approach involving (1) history of specific continent or country of travel, (2) exposure to specific environments (forests or farms, water sports, consumption of exotic foods), (3) incubation period, and (4) pattern of organ involvement and subtle differences in manifestations help in differential diagnosis and choice of initial empiric therapy. Fever, rash, hypotension, thrombocytopenia and mild derangement of liver function tests is seen in a majority of patients. Organ failure may lead to shock, respiratory distress, renal failure, hepatitis, coma, seizures, cardiac arrhythmias or hemorrhage. Diagnosis in some conditions is made by peripheral blood smear examination, antigen detection or detection of microbial nucleic acid by PCR. Tests that detect specific IgM antibody become positive only in the second week of illness. Initial therapy is often empiric; a combination of intravenous artesunate, ceftriaxone and either doxycycline or azithromycin would cover a majority of the treatable syndromes. Additional antiviral or antiprotozoal medications are required for some specific syndromes. Involving a physician specializing in tropical or travel medicine is helpful.

Topics: Artesunate; Azithromycin; Ceftriaxone; Child; Communicable Diseases; Critical Care; Dengue; Diagnosis, Differential; Doxycycline; Exanthema; Female; Fever; Geography; Humans; Intensive Care Units; Leptospirosis; Malaria; Male; Nervous System Diseases; Pregnancy; Shock, Hemorrhagic; Syndrome; Travel; Tropical Medicine; Typhoid Fever

Acute central nervous system (CNS) infections in children in sub-Saharan Africa are often fatal. Potential contributors include late presentation, limited diagnostic capacity and inadequate treatment. A more nuanced understanding of treatment practices with a goal of optimizing such practices is critical to prevent avoidable case fatality. We describe empiric antimicrobial treatment, antibiotic resistance and treatment adequacy in a prospective cohort of 459 children aged two months to 12 years hospitalised for suspected acute CNS infections in Mbarara, Uganda, from 2009 to 2012. Among these 459 children, 155 had a laboratory-confirmed diagnosis of malaria (case-fatality rate [CFR] 14%), 58 had bacterial infections (CFR 24%) and 6 children had mixed malaria and bacterial infections (CFR 17%). Overall case fatality was 18.1% (n = 83). Of 219 children with laboratory-confirmed malaria and/or bacterial infections, 182 (83.1%) received an adequate antimalarial and/or antibiotic on the day of admission and 211 (96.3%) within 48 hours of admission. The proportion of those receiving adequate treatment was similar among survivors and non-survivors. All bacterial isolates were sensitive to ceftriaxone except one Escherichia coli isolate with extended-spectrum beta-lactamase (ESBL). The observed high mortality was not a result of inadequate initial antimicrobial treatment at the hospital. The epidemiology of CNS infection in this setting justifies empirical use of a third-generation cephalosporin, however antibiotic resistance should be monitored closely.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; beta-Lactamases; Ceftriaxone; Central Nervous System Infections; Child; Child, Preschool; Coinfection; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; Humans; Infant; Malaria; Male; Uganda

Widespread empiric use of antibiotics exists especially in developing countries. This is a concern since inappropriate use of antibiotics, including their extended inappropriate use, will increase resistance rates. Consequently, there is a need to evaluate antibiotic utilisation across healthcare sectors to improve future use. This includes ceftriaxone, widely used among hospitals including those in Ghana.. A cross-sectional study to evaluate the appropriateness of ceftriaxone prescribing in a leading hospital in Ghana. Ceftriaxone prescribing in patient-record cards was assessed using a modified WHO drug-utilization evaluation criteria as well as referencing the national standard treatment guidelines in Ghana and the ceftriaxone package insert.. A total of 251 patients were assessed. Ceftriaxone was most commonly prescribed for comorbid malaria with bacterial infections, urinary tract infections, sepsis and gastroenteritis. The appropriateness of the indication was 86% (n = 218). The doses most prescribed were 1g (41%) and 2g (39%). Stat dose and once-daily dosage regimen constituted 51.4% and 84.5%, respectively. The most common duration of treatment was 1 (51.4%) and 2 days (35.1%). The overall appropriateness of prescribing was 93% against a pre-set threshold of 97%.. The appropriateness of ceftriaxone prescribing was high in this leading hospital in Ghana; however, there is room for improvement with targeted education initiatives, with further research planned.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Bacterial Infections; Ceftriaxone; Child; Child, Preschool; Coinfection; Cross-Sectional Studies; Drug Utilization Review; Female; Ghana; Humans; Infant; Injections; Malaria; Male; Middle Aged; Pharmacy Service, Hospital; Pilot Projects; Young Adult

In sub-Saharan Africa, non-typhoidal Salmonella (NTS) can cause bloodstream infections, referred to as invasive non-typhoidal Salmonella disease (iNTS disease); it can occur in outbreaks and is often preceded by malaria. Data from Central Africa is limited.. Clinical, microbiological and molecular findings of NTS recovered in a blood culture surveillance project (2009-2014) were analyzed.. In March-July 2012 there was an epidemic increase in malaria infections in the Oriental Province of the Democratic Republic of the Congo (DRC). In one referral hospital, overall hospital admissions in June 2012 were 2.6 times higher as compared to the same period in the years before and after (336 versus an average of 128 respectively); numbers of malaria cases and blood transfusions were nearly three- and five-fold higher respectively (317 versus 112 and 250 versus 55). Case fatality rates (in-hospital deaths versus all admissions) peaked at 14.6 %. Salmonella Typhimurium and Salmonella Enteritidis together accounted for 88.9 % of pathogens isolated from blood cultures collected during an outreach visit to the affected districts in June 2012. Children infected with Salmonella Enteritidis (33 patient files available) tended to be co-infected with Plasmodium falciparum more often than children infected with Salmonella Typhimurium (40 patients files available) (81.8 % versus 62.5 %). Through the microbiological surveillance project (May 2009-May 2014) 113 unique NTS isolates were collected (28.5 % (113/396) of pathogens); most (95.3 %) were recovered from children < 15 years. Salmonella Typhimurium (n = 54) and Salmonella Enteritidis (n = 56) accounted for 47.8 % and of 49.6 % NTS isolates respectively. Multilocus variable-number tandem-repeat analysis (MLVA) revealed more heterogeneity for Salmonella Typhimurium than for Salmonella Enteritidis. Most (82/96, 85.4 %) NTS isolates that were available for antibiotic susceptibility testing were multidrug resistant. All isolates were susceptible to ceftriaxone and azithromycin.. During the peak of an epidemic increase in malaria in the DRC in 2012, a high proportion of multidrug resistant Salmonella Typhimurium and Salmonella Enteritidis were isolated from blood cultures. Overall, the two serovars showed subtle differences in clinical presentation and genetic diversity.

Topics: Adolescent; Adult; Anti-Bacterial Agents; Asian People; Azithromycin; Bacteremia; Ceftriaxone; Child; Child, Preschool; Coinfection; Democratic Republic of the Congo; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Female; Hospitalization; Humans; Infant; Infant, Newborn; Malaria; Malaria, Falciparum; Male; Salmonella enteritidis; Salmonella Infections; Salmonella typhimurium; Serogroup; Tandem Repeat Sequences

An increasing number of travelers from western countries visit tropical regions, questioning western physicians on the prophylaxis, the diagnosis and the therapeutic management of patients with travel-associated infection. In July 2014, a French couple stayed for an adventure-travel in Columbia without malaria prophylaxis. A week after their return the woman presented with fever, myalgia, and retro-orbital pain. Three days later, her husband presented similar symptoms. In both patients, testing for malaria, arboviruses and blood cultures remained negative. An empirical treatment with doxycycline and ceftriaxone was initiated for both patients. Serum collected from the female patient yielded positive IgM for leptospirosis but was negative for her husband. Positive Real-Time PCR were observed in blood and urine from both patients, confirming leptospirosis. Three lessons are noteworthy from this case report. First, after exclusion of malaria, as enteric fever, leptospirosis and rickettsial infection are the most prevalent travel-associated infections, empirical treatment with doxycycline and third generation cephalosporin should be considered. In addition, the diagnosis of leptospirosis requires both serology and PCR performed in both urine and blood samples. Finally, prophylaxis using doxycycline, also effective against leptospirosis, rickettsial infections or travellers' diarrhea should be recommended for adventure travelers in malaria endemic areas.

Topics: Adult; Anti-Bacterial Agents; Ceftriaxone; Colombia; Diagnosis, Differential; Doxycycline; Female; Fever; France; Humans; Leptospirosis; Malaria; Male; Rickettsia Infections; Travel; Treatment Outcome; Typhoid Fever

According to current estimates, Plasmodium malariae is not very common in Senegal, as more than 98% of malaria cases are suspected to be due to Plasmodium falciparum. However, it is possible that other malarial species are being under-reported or misdiagnosed. This is a report of a case of P. malariae in a 30-year-old man previously hospitalized with acute kidney injury after treatment with quinine and re-hospitalized three months later. He was diagnosed with renal cortical necrosis post malaria treatment. Plasmodium malariae was identified with light microscope and confirmed using species-specific small-subunit rRNA (ssrRNA) amplification.The patient was treated for malaria with intravenous quinine for seven days, followed by three days of oral treatment; the bacterial infection was treated using ceftriaxone during the first hospitalization and ciprofloxacin associated with ceftriaxone the second time. He also had four rounds of dialysis after which he partially recovered the renal function. Given the complications that can be caused by P. malariae infection, it should be systematically looked for, even if the predominant species is P. falciparum in Senegal.

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Antimalarials; Bacterial Infections; Ceftriaxone; Humans; Malaria; Male; Microscopy; Nucleic Acid Amplification Techniques; Plasmodium malariae; Quinine; Renal Dialysis; RNA, Ribosomal, 18S; Senegal; Treatment Outcome

Nontyphoidal Salmonella (NTS) is recognized as a common cause of bacteremia in malaria-endemic Africa but its importance as a cause of pneumonia is uncertain. We report a case of pneumonia caused by NTS confirmed by culture of lung aspirate from a consolidated left lung in a 16 month-old HIV-uninfected girl who had been admitted to the hospital 1 month previously with severe malaria. She did not respond to first-line antibiotic therapy for benzylpenicillin and gentamicin but improved with ceftriaxone therapy.

Topics: Anti-Bacterial Agents; Ceftriaxone; Female; Gentamicins; HIV Infections; Hospitalization; Humans; Infant; Lung; Malaria; Malawi; Penicillin G; Pneumonia, Bacterial; Salmonella; Salmonella Infections

On December 26, 2004, a tsunami from the Indian Ocean struck the coastal city of Banda Aceh, Sumatra, Indonesia. This case report describes a 24-year-old woman who presented to the Dr. Zainoel Abidin Hospital in Banda Aceh on January 8, 2005, with a tsunami-related illness. The patient was initially treated for tetanus and aspiration pneumonia with a guarded prognosis. Her recovery was complicated by malaria and recurrent pneumonia. Treatment was hampered by a shortage of medication and equipment, damage to the hospital, and a filthy environment. Morphine, diazepam, and ketamine infusions were used to good effect. This case highlights some of the logistical problems of treating multiple tetanus patients in an austere environment.

Topics: Adult; Ceftriaxone; Diazepam; Disasters; Female; Humans; Indonesia; Malaria; Metronidazole; Pneumonia; Prognosis; Tetanus

Topics: Adult; Animals; Antimalarials; Ceftriaxone; Humans; Lyme Disease; Malaria; Male; Plasmodium malariae