21.2 Multisystemic Infections I: Septicemia, Septicopyemia & Septic Shock, Leptospirosis and Schistosomiasis japonica

Why this area matters

The TOS multisystemic area lists:

• septicemia and septicopyemia;
• HIV/AIDS.

Sepsis is a leading cause of death in Philippine hospitals, from community pneumonia, urinary and abdominal infections to newborn sepsis. Leptospirosis surges after every typhoon and flood. Schistosomiasis is endemic in farming communities in the Visayas and Mindanao. Board questions test current sepsis definitions, the first hour of management, organisms in special hosts, leptospirosis risk categories and prophylaxis, and the schistosome life cycle.

Definitions

• Bacteremia: bacteria in the bloodstream, which may be transient, as after tooth brushing.
• Septicemia: the older clinical term for systemic illness caused by microorganisms and their toxins circulating in the blood.
• Septicopyemia (pyemia): septicemia with septic emboli that seed metastatic abscesses in the lungs, kidneys, spleen, bones, joints and brain. It is classically caused by Staphylococcus aureus.
• Sepsis (Sepsis-3, 2016):
  • life-threatening organ dysfunction caused by a dysregulated host response to infection;
  • organ dysfunction means an acute rise of 2 points or more in the SOFA score;
  • the bedside qSOFA prompts closer assessment: respiratory rate of 22 or more, altered mentation, systolic BP of 100 or less.
• Septic shock: sepsis needing vasopressors to keep mean arterial pressure at 65 mmHg or more and with serum lactate above 2 mmol/L despite adequate fluid resuscitation. Mortality exceeds 40%.

Pathogenesis of sepsis

• Microbial products are recognized by pattern-recognition receptors:
  • lipopolysaccharide (lipid A) through TLR4;
  • peptidoglycan and lipoteichoic acid through TLR2;
  • flagellin through TLR5.
• Cytokines (TNF-alpha, IL-1, IL-6) and complement then:
  • cause fever and vasodilation;
  • increase capillary leak;
  • activate tissue factor, producing disseminated intravascular coagulation.
• Later phase: immunosuppression follows, with secondary infections.
• Superantigens (TSST-1, streptococcal pyrogenic exotoxins) bind MHC class II and T-cell receptors outside the antigen groove, activating up to 20% of T cells and causing a cytokine storm.
  • Staphylococcal toxic shock syndrome (retained tampons, nasal packing, wounds) causes fever, a diffuse sunburn-like rash that later peels, hypotension and multiorgan involvement; blood cultures are often negative.
  • Streptococcal toxic shock syndrome often accompanies necrotizing fasciitis, and blood cultures are positive.

Special hosts and organisms

• Meningococcemia: rapid petechiae and purpura, shock and Waterhouse-Friderichsen syndrome (bilateral adrenal hemorrhage).
• S. aureus bacteremia:
  • always obtain repeat blood cultures and an echocardiogram to look for endocarditis;
  • remove infected devices;
  • give at least 14 days of IV therapy, longer if metastatic foci are present.

The first hour of sepsis care

The Surviving Sepsis Campaign (2021) recommends:

• take blood cultures (two sets) before antibiotics, but do not delay antibiotics;
• give broad-spectrum antibiotics within 1 hour for probable septic shock or sepsis;
• give 30 mL/kg of crystalloid within the first 3 hours for hypotension or lactate of 4 mmol/L or more, guided by dynamic reassessment;
• start norepinephrine as the first-line vasopressor to keep MAP at 65 mmHg or more;
• measure lactate and repeat it if raised;
• find and control the source: drain abscesses, relieve obstruction and remove infected devices.

Endemic Zoonotic & Spirochetal Pathogens

Leptospira interrogans & Philippine Post-Flood Prophylaxis Guidelines

Leptospira interrogans is an obligate aerobe, thin, tightly coiled spirochete with distinct hooked ends (resembling ice tongs or a question mark), visualized via darkfield microscopy and confirmed by the Microscopic Agglutination Test (MAT). In the Philippines, leptospirosis is a major public health emergency, peaking during monsoon season when urban flooding (such as across Metro Manila) forces residents and rescue workers to wade through waters contaminated with urine from infected rodents.

Clinical Presentation & Weil Disease

Leptospirosis follows a biphasic clinical course:

1. Leptospiremic (Anicteric) Phase: Abrupt onset of high fever, severe headache, intense myalgia predilecting for the calves and lumbar region, and pathognomonic bilateral conjunctival suffusion without purulent discharge.
2. Immune Phase: Appearance of IgM antibodies accompanied by systemic vascular endothelial damage. In a minority of cases, this progresses to Weil disease, the term now used for severe leptospirosis with fever, jaundice and renal failure (often non-oliguric with hypokalemia), commonly with bleeding. Pulmonary hemorrhage is a leading cause of death.

Philippine DOH Leptospirosis Prophylaxis Guidelines

Source: Leptospirosis Task Force, Leptospirosis CPG 2010 (adopted in the PhilHealth leptospirosis policy statements). Prophylaxis requires a physician's prescription, and people given it should still watch for fever because it is not 100% effective.

Doxycycline cautions: doxycycline should not be given in pregnancy or to children younger than 8 years and passes into breast milk. The CPG states that there is no recommended pre-exposure prophylaxis that is safe for pregnant and lactating women. For pre-exposure prophylaxis in non-pregnant adults with short-term exposure (for example, soldiers or rescuers), the regimen is doxycycline 200 mg once weekly, starting 1 to 2 days before exposure and continuing throughout it.

Diagnosis and Treatment Under the 2010 CPG

• Suspected case: a history of exposure (wading in floods or contaminated water, contact with animal fluids, swimming in floodwater, or ingesting contaminated water) plus at least two of myalgia, calf tenderness, conjunctival suffusion, chills, abdominal pain, headache, jaundice or oliguria.
• Incubation period: 2 to 28 days.
• Laboratory confirmation: a four-fold rise in the microscopic agglutination test (MAT) titer between acute and convalescent sera, or in endemic areas such as the Philippines a single MAT titer of at least 1:1600 in a symptomatic patient. IgM rapid tests are less sensitive in the first week (about 63% to 72%) and improve after day 7.
• Mild leptospirosis (outpatient): doxycycline 100 mg twice daily for 7 days; alternatives are amoxicillin or azithromycin.
• Moderate to severe leptospirosis (hospital): any of jaundice, oliguria or anuria, meningismus, sepsis or septic shock, altered mental state, difficulty of breathing or hemoptysis. The drug of choice is IV penicillin G; alternatives are IV ampicillin, ceftriaxone or cefotaxime, or IV azithromycin.

Schistosomiasis japonica

Schistosoma japonicum (Oriental Blood Fluke)

Schistosoma japonicum is the only human blood fluke endemic to the Philippines. It is endemic in 28 provinces in 12 regions, mainly in Leyte, Samar, Sorsogon, Oriental Mindoro, Bohol and many provinces of Mindanao.

Intermediate Host & Life Cycle

The obligate intermediate host in the Philippines is the tiny, amphibious, operculated freshwater snail Oncomelania hupensis quadrasi, which lives in damp vegetation along irrigation ditches, unlined canals, and rice paddies. Miracidia excreted in human or animal feces penetrate Oncomelania snails, multiplying into fork-tailed, free-swimming cercariae. Cercariae emerge into fresh water and actively penetrate the unbroken skin of agricultural laborers and farmers wading in rice paddies. They transform into schistosomulae, enter the venous system, migrate through the lungs to the portal vein, mature into adult worms, and pair in copula within their definitive habitat: the inferior and superior mesenteric venules draining the colon and small intestine.

Egg Morphology & Kato-Katz Diagnostic Standard

Adult female worms produce 500 to 2,000 eggs daily. The egg is subspherical to broadly oval ($70-100 \times 50-70\text{ um}$) with a smooth, thin shell and a minute, rudimentary lateral knob or spine (often difficult to visualize under light microscopy and never exhibits the prominent lateral spine of S. mansoni or terminal spine of S. haematobium). The diagnostic standard of choice is the Kato-Katz thick smear technique on stool; circumoval precipitin testing (COPT) and rectal mucosal biopsy are used for chronic or low-intensity cases.

Pathology: Symmers' Pipe-Stem Periportal Fibrosis

A large proportion of eggs fail to pass into the intestinal lumen, instead being carried retrograde via the portal blood flow into the liver, where they lodge within presinusoidal periportal venules. Secreted soluble egg antigens trigger intense CD4 Th2-mediated granulomatous inflammation, followed by extensive periportal collagen deposition. This produces pathognomonic Symmers' pipe-stem periportal fibrosis, visible on ultrasound as dense hyperechoic cuffs encircling portal vein branches.

Because fibrosis is strictly presinusoidal, it produces severe portal hypertension, massive splenomegaly, hypersplenism, caput medusae, and life-threatening bleeding from esophageal varices. Crucially, hepatocellular synthetic function (serum albumin, prothrombin time, transaminases) remains remarkably preserved until late end-stage disease, distinguishing schistosomal fibrosis from cirrhosis.

Pharmacotherapy

The drug of choice is Praziquantel (60 mg/kg orally), administered in two or three divided doses over a single day.

Additional points on schistosomiasis:

• S. japonicum is a true zoonosis. Carabao, cattle, dogs, pigs and rats also excrete eggs, which makes control harder than for human-only schistosomes.
• Acute schistosomiasis (Katayama fever) follows heavy first exposure. It brings fever, urticaria, hepatosplenomegaly and eosinophilia as egg-laying begins.
• Cercarial dermatitis ("swimmer's itch") is an itchy papular rash at the site of skin penetration.
• Ectopic eggs in the brain cause seizures. S. japonicum is the schistosome most often associated with cerebral involvement.
• Control combines:
  • mass treatment with praziquantel in endemic barangays;
  • snail control, such as clearing and lining irrigation canals;
  • sanitation, so that feces do not reach fresh water;
  • footwear and protective clothing for farmers;
  • treatment of infected animals.