Highlights: (1) Blood culture is the gold standard for the diagnosis of bacterial infections. (2) Bone marrow culture is more sensitive than blood culture even in patients with enteric fever receiving antibiotics. (3) Microscopic agglutination test is considered the gold standard for diagnosing leptospirosis; however, now IgM ELISA and polymerase chain reaction (PCR) are more frequently used for diagnosis. (4) Tuberculosis is diagnosed with the help of nucleic acid amplification tests like Xpert MTB/RIF Ultra which also detects rifampicin resistance. Other tests include microscopy, Lowenstein–Jensen and mycobacteria growth indicator tube culture, line probe assay. (5) Tropical rickettsial infections are diagnosed by serological reactions (Weil–Felix, ELISA for antibodies) and PCR. (6) For Brucellosis culture from blood, bone marrow or tissue specimens remain the mainstay in diagnosis. (7) Dengue, Zika, Crimean–Congo hemorrhagic fever, Ebola, hantavirus, rabies are diagnosed with reverse transcriptase-polymerase chain reaction. Serological tests like IgM ELISA or paired sera samples for IgG are also used for diagnosis.
Most cases of severe malaria are caused by Plasmodium falciparum. Severe malaria is characterized by severe organ dysfunction. Both peripheral smear examination and rapid diagnostic test have a role in the diagnosis. Parenteral artesunate is clearly the drug of choice for the management of severe malaria. Parenteral artesunate should always be followed up with ACT.
Most of the complications of severe malaria require supportive care only. The role of exchange transfusions in the management of severe malaria is questionable in the postartesunate era. Malaria in pregnancy can be quite severe and artesunate is now the drug of choice for all three trimesters. Vivax malaria is being increasingly recognized as a cause of severe malaria. The cause for this increased virulence is still not clear. Management of severe vivax malaria is similar to that of severe falciparum malaria.
Tropical infections constitute 20 – 30% of intensive care unit (ICU) admissions in developing countries. Leptospirosis is a spectrum with mild form presenting as an acute febrile illness with jaundice, complicating in few as acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC), and multi-organ dysfunction syndrome (MODS). The poor prognostic markers are hemorrhagic ARDS, acute renal failure, DIC, severe metabolic acidosis, older age, chronic alcohol abuse, high SOFA score, and septic shock. The confirmatory diagnosis relies on antibody testing, such as microscopic agglutination test (MAT) and IgM ELISA, while the reverse transcription-polymerase chain reaction test being reserved for clinically suspected antibody negative cases. The spectrum of multi-organ involvement necessitates a complete hematological, biochemical workup, including electrocardiogram (ECG), chest X-ray, and two-dimensional echocardiography. Specific antimicrobial therapy consists of the following—benzylpenicillin, ceftriaxone, cefotaxime, and doxycycline. The reported mortality ranges from 6% to as high as 44%. Various ICU scores like SPiRO, THAI LEPTO score, and Faine's criteria have been useful in risk stratification. Optimizing intensive care treatment with appropriate antibiotics, lung protection ventilation strategies, strict fluid management, and if need be timely initiation of renal replacement therapy (RRT) helps in reducing mortality.
George M. Varghese
Scrub typhus and other rickettsial infections contribute to 25 – 50% of acute undifferentiated febrile illnesses in endemic regions. Delayed recognition and therapy increase the morbidity and mortality. The constellation of fever with eschar or rash and multisystem involvement should facilitate the diagnosis and initiation of appropriate therapy. The pathological hallmark of rickettsial infections is endothelial infection and inflammation causing vasculitis. Endothelial inflammation results in microvascular dysfunction and increased vascular permeability. Immune and endothelial activation may worsen microvascular dysfunction, predisposing to multi-organ failure. Serology is the mainstay of diagnosis, although false negatives occur early in the disease. Point-of-care rapid diagnostic tests and molecular techniques, such as quantitative polymerase chain reaction (qPCR), can hasten diagnostic processes. Intravenous doxycycline with a loading dose is the most widely used antibiotic in critically ill patients, with azithromycin as a suitable alternative. Early appropriate treatment and organ support can decrease the duration of illness and be life-saving.
Enteric fever (typhoid and paratyphoid)is caused by Salmonella typhiandSalmonella paratyphi. It is spread by fecal-oral route, largely through contamination of water and foodstuff. Developing countries are the worst affected. It takes 7 – 21 days from ingestion of the organism to manifestation of symptoms which are generally Fever, relative bradycardia, and pain abdomen. Hepatosplenomegaly, intestinal bleeding, and perforation are the features at various stages of the disease. The bacteria invade the submucous layer and proliferate in the Payer's patches. Blood culture is the gold standard for diagnosis but it is only rarely positive. Fluroquinolones, cephalosporins, and azithromycin are antibiotics of choice. There is increasing evidence of the development of resistance to all antibiotics. Salmonella sepsis, though uncommon, can occur.Intestinal perforation, peritonitis, and secondary sepsis are complications that may require intensive care unit management.
About 3.4% of the hospitalized tubercular patients need admission to the intensive care unit (ICU). Patients requiring ICU admission had a poor prognosis and high mortality rate (60 vs 25%) as compared to other causes of severe pneumonia. The most common indication for tuberculosis-related ICU admission is acute respiratory failure due to pneumonia or acute respiratory distress syndrome (ARDS) (with or without miliary tuberculosis) followed by septic shock with multiple organ dysfunction, adrenal insufficiency, and neurological involvement, especially tubercular meningitis. Tuberculosis patients who require admission to ICU are mostly immunocompromised [human immunodeficiency virus (HIV) coinfection] and have underlying miliary tuberculosis or disseminated tuberculosis. Pulmonary tuberculosis presenting as ARDS is a rare phenomenon, but a most common cause of admission of tuberculosis patients to ICU. Tuberculous meningitis is the most severe form of tuberculosis with mortality more than 60% and residual neurological disability in 25% cases. Tuberculosis-related septic shock has been found in only 1% of all septic shock patients admitted to ICU. Patients with tuberculosis with refractory shock should be suspected for adrenal insufficiency. A trial of physiologic stress replacement dose of hydrocortisone (200–300 mg) should be given to all critically ill patients with vasopressor-dependent shock after correcting other causes. Diagnosis and treatment of tuberculosis in critically ill patients has various challenges, namely appropriate sample collection, issues with the route of administration, drug absorption, bioavailability, dose modification in hepatic and renal dysfunction, and interaction with other drugs.
• Tetanus is caused by an exotoxin, tetanospasmin, produced by Clostridium tetani, an anaerobic gram-positive bacillus.
• Tetanospasmin prevents the release of inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the spinal cord, brainstem motor nuclei, and the brain, producing muscle rigidity and tonic spasms.
• Trismus (lockjaw), dysphagia, laryngeal spasms, rigidity of limbs and paraspinal muscles, and opisthotonic posture are common.
• Frequent severe spasms triggered by touch, pain, bright light, or sounds may produce apnea and rhabdomyolysis.
• Autonomic overactivity occurs in severe tetanus causing labile hypertension, tachycardia, increased secretions, sweating, and urinary retention. Dysautonomia is difficult to manage and is a common cause of mortality; magnesium sulfate infusion is often used.
• Antibiotics (penicillin or metronidazole) and wound care reduce toxin production and human tetanus immune globulin neutralizes the circulating toxin.
• Nasogastric tube placement for feeding and medications is needed.
• Early elective tracheostomy is performed in moderate or severe tetanus to prevent aspiration and laryngeal stridor.
• Benzodiazepines help reduce rigidity, spasms, and autonomic dysfunction. Large doses of diazepam (0.2–1 mg/kg/h) are administered via nasogastric tube.
• Neuromuscular blocking agents and mechanical ventilation are used for refractory spasms.
• Mortality ranges from 5% to 50%.
Key Points: (1) Diabetes, hazardous alcohol use, and/or significant heart disease are more likely to develop a critical illness with melioidosis. (2) Pneumonia is the most common presentation. Those with pneumonia or bacteremia are most likely to require intensive care unit admissions. (3) Culture is the mainstay for the diagnosis. However, it is noted that Burkholderia pseudomallei is often wrongly identified as Pseudomonas or other Burkholderia species by commonly available commercial techniques. (4) Therapy consists of an intensive phase with intravenous antibiotics to prevent mortality followed by an eradication phase with oral antibiotics to prevent relapse. (5) Meropenem is the drug of choice for those with septic shock or neurological involvement. For patients with nonpulmonary organ focal sites of infection (neurologic, prostatic, bone, joint, cutaneous, and soft tissue melioidosis), the addition of trimethoprim-sulfamethoxazole (TMP-SMX) to ceftazidime/carbapenem during intensive therapy is recommended. TMP-SMX is the drug of choice for oral antibiotic therapy during the eradication phase. (6) Adequate source control is essential for successful treatment and to prevent relapse. (7) The use of granulocyte-colony stimulating factor (G-CSF) those with septic shock is controversial.
Leishmaniasis is one of the chronic debilitating vector-borne diseases caused by obligate intracellular protozoa. The global burden of disease although not increasing but potential risk of spread is there. At least 20 species of Leishmania are pathogenic to human beings. The transmission is from female sandfly through a blood meal. The disease pathogenesis is dependent on parasite and host mechanism—primarily cell-mediated immunity. The three common forms are visceral, cutaneous, and mucocutaneous. The diagnostic tests are mainly based on aspiration from the spleen or bone marrow. The use of K39 antibodies is the best serodiagnostic test. Antimonial, amphotericin B, miltefosine, and paromomycin are the drugs used to treat leishmaniasis. Amphotericin therapy shows the response within 7 to 10 days in most subjects, and 2 weeks of therapy is sufficient. However, those going into relapse need new treatment regimes. There is a definite benefit of combination therapy. However, there is still no breakthrough on a vaccine for prophylaxis.
Vinita E Mani,
RNA viruses are not only reported for viral pandemics but also as important agents for emerging/re-emerging diseases. Japanese encephalitis virus (JEV) is reported to cause epidemics of encephalitis in Southeast Asia, India, Korea, China, and Indonesia. In addition, several reports show that JEV has spread to new populations beyond these geographical regions. The disease mostly affects children with a mortality rate up to 30%. In peridomestic settings, pigs are reported as amplifiers of JEV transmission and aquatic birds as maintenance hosts of the virus. The Culex mosquito is the vector for transmission of JEV. This virus is a member of the family Flaviviridae and has a single-stranded positive-sense RNA virus. Five different genotypes (G-I to G-V) of JEV have been reported. Four different kinds of vaccines have been produced to prevent JEV infection. However, there is no FDA-approved antiviral drug available for JEV.
In the modern era, the relative ease and faster speed of travel have made the world a global village. An increasing number of people are traveling to distant and sometimes exotic locations for vacation/leisure or at times for business purposes. Along with the experiences of far-fetched lands, sometimes they bring bugs/organisms that are not native to their motherland. This makes the diagnosis and management of illnesses in a traveler challenging. In this review, we have tried to outline a management protocol for travelers returning with fever, with specific emphasis on trypanosomiasis and schistosomiasis.
The choice of statistical test used for analysis of data from a research study is crucial in interpreting the results of the study. This article gives an overview of the various factors that determine the selection of a statistical test and lists some statistical tests used in common practice.