Table 5 Summary of acute haemolysis reports, Jiangsu province

Case series[38]

Setting: 1975, Jinhu county, Huaiyin prefecture, 254,910 residents given primaquine (22.5 mg daily × 8 days) and pyrimethamine (50 mg daily × 2 days), Incidence of haemolysis: 3.5/100,000

Baseline characteristics of affected patients: 8 of 9 were male, mean age 14.4 (range 5 to 38), two brothers with history of favism.

Methods: clinical course described in nine patients with acute haemolysis

Haemolysis on day 2 or 3 after cumulative dose of 45 mg in 2 adults and after 15-30 mg in children (ages 5 to 15)

Symptoms: haematuria, weakness, fever, appetite loss, abdominal pain/discomfort, dizziness and headache, bruising, epistaxis

Patients recovered with drug discontinuation, transfusions, and supportive care

Case series[39]

Setting: 1976, Linhe county, Nanjing prefecture, 444,589 residents given primaquine (30 mg daily × 4 days) and pyrimethamine (50 mg daily × 2 days), Incidence of haemolysis: 9.3/100,000

Baseline characteristics of affected patients: 32 of 40 were male, age range 4 to 62, 65% were <15 y, 20% with history of favism, 15% with family history of haemolysis

Methods: collected clinical data in 40 patients with acute haemolysis (more detailed data from 18 hospitalized patients), methaemoglobin reductive testing in 80 family members (immediate and spouse) and 29 healthy controls

Haemolysis in 18 hospitalized patients: 56% onset 1-2 days after medication. Haemoglobin levels (g/dL): 3-5: 12 patients, 5.2-6.5: 7 patients, 7.5: 1 patient (unclear if repeated measured included)

Symptoms: jaundice (18), fever (17), loss of appetite (14), weakness (12), dizziness (11), haematuria (9), dark coloured urine (8), abdominal pain (7), cyanosis (7), and headache (7)

Deficiency by methaemoglobin testing: 65% of patients tested one month after haemolytic event, 28/50 (56%) female family including 12 of 29 mothers tested and 11 of 17 mothers of male patients, 6/30 (20%) male family (age range of male or female family members: 6-70 y), 0% in adult controls (53.8% male); deficiencies were medium except severe in 2 patients and 2 family members

Household clustering rare (1 household with 3 cases, 2 households with 2 cases)

Cross-sectional survey[40]

Setting: as above Methods; methaemoglobin reductive testing in family members of 3 patients who had haemolysis after primaquine, 94/141 family members agreed to participate

Deficiency by methaemoglobin testing detected in 59.6%. Test results by sex (males n = 54, females n = 40): any deficiency: 51.9% in males vs 70.0% in females, serious deficiency: 51.9% in males vs 17.5% in females

Cross-sectional survey[41]

Setting: as above but in 1977 following mass drug administration Methods: methaemoglobin reductive testing in 1515 subjects from 4 comparison groups Comparison groups: 1) village with high incidence of haemolysis, 2) village with past P. falciparum cases, 3) village with Hui minority group, 4) patients with schistosomiasis associated liver disease or chronic hepatitis. All ≥5 years of age

Prevalence of deficiency: group 1: 5.7% (60/1051, 19 severe), group 2: 3/289 1.0% (1 severe), group 3: 0.7% (1/143), group 4 0% (0/32)

Prevalence of deficiency by sex: males 4.9% vs females 3.8% (n=689 males and 801 females). Prevalence of deficiency in males by age: 5-9y 10.5% (n = 58), 10-14y 5.8% (n = 220), 15-18y 3.5% (n = 114), 19-30y 2.3% (n = 131), 31-60y 5.2% (n = 153), >60y 0.0% (n = 13). Prevalence of deficiency in females by age: 5-9y 9.7% (n = 62), 10-14y 3.5% (n = 170), 15-18y 2.5% (n = 120), 19-30y 2.5% (n = 303), 31-60y 4.5% (n = 224), >60y 0.0% (n = 22)

Case report[42]

Setting: 1979, Xinyi county, Xuzhou prefecture Methods: clinical course described

15 y male diagnosed with vivax malaria based on clinical symptoms of fever, sweats, headache. Developed fever and malaise after 2 days of chloroquine (900 mg) and primaquine (37.5 mg), next day had dark urine, jaundice, nausea, vomiting, fever, hepatomegaly, haematocrit 35%. Admitted and recovered with discontinuation of primaquine, transfusions, and supportive care.