Publications

Primaquine is an 8-aminoquinoline antimalarial. It is the only widely available treatment to prevent relapses of Plasmodium vivax malaria. The 8-aminoquinolines cause dose dependent haemolysis in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals. G6PDd is common in malaria endemic areas but testing is often not available. As a consequence primaquine is underused.We conducted a pharmacometric study to characterise the relationship between primaquine dose and haemolysis in G6PDd. The aim was to explore shorter and safer primaquine radical cure regimens compared to the currently recommended 8-weekly regimen (0.75 mg/kg once weekly), potentially obviating the need for G6PD testing. Hemizygous G6PDd healthy adult Thai and Burmese male volunteers were admitted to the Hospital for Tropical Diseases in Bangkok. In Part 1, volunteers were given ascending dose primaquine regimens whereby daily doses were increased from 7.5 mg up to 45 mg over 15 to 20 days. In Part 2, a single primaquine 45 mg dose was given.24 volunteers were enrolled in Part 1, and 16 in Part 2 (13 participated in both studies). In three volunteers, the ascending dose regimen was stopped because of haemolysis (n=1) and asymptomatic increases in transaminases (n=2; one was hepatitis E positive). Otherwise the ascending regimens were well tolerated with no drug-related serious adverse events. In Part 1, the median haemoglobin concentration decline was 3.7 g/dL (range: 2.1 to 5.9; relative decline of 26% [range: 15 to 40%]). Primaquine doses up to 0.87 mg/kg/day were tolerated subsequently without clinically significant further falls in haemoglobin. In Part 2, the median haemoglobin concentration decline was 1.7 g/dL (range 0.9 to 4.1; relative fall of 12% [range: 7 to 30% decrease]). The ascending dose primaquine regimens gave 7 times more drug but resulted in only double the haemoglobin decline.In patients with Southeast Asian G6PDd variants full radical cure treatment can be given in under three weeks compared with the current 8 week regimen.

The in vitro activities of 14 antimicrobial agents were determined for 78 strains of Yersinia pestis. The most active antibiotics were ceftriaxone and ciprofloxacin, followed by ofloxacin and ampicillin. The agents traditionally used for the treatment of plague (streptomycin, tetracycline, and chloramphenicol) were considerably less active. Azithromycin showed poor activity against all strains.

LONG‐STANDING TIES Canada and South Asia: Political and Strategic Relations, Arthur C. Rubinoff (editor), The Centre for South Asian Studies, The Universitty of Toronto, Toronto, 1993, pages 150. SON'S TRIBUTE Rajagopalachari: A Biography, C. R. Narasimhan, Sangam Books Ltd, London, 1993, pages xiii + 263, £19.95. TOWARDS EUROPEAN UNION European Political Co‐operation, Simon J. Nuttall, Clarendon Press, Oxford, pages 342, £35.00. CONTENTIOUS REGION The Crackdown in Kashmir: Torture of Detainees and Assaults on the Medical Community. An Asia Watch Report, Patricia Gossman and Vincent Iacopino, Human Rights Watch, New York, 1993, US $7.00, pages 41. A GOOD PLACE TO LIVE? Historical Dictionary of Hong Kong and Macau, Elfed Vaughan Roberts, Sum Ngai Ling and Peter Bradshaw, The Scarecrow Press, Metuchen, NJ and London, 1992, pages 355, £49.50. Hong Kong, C. P. Lo, Belhaven Press, London, 1992. DECLINE AND FALL The Fall of Imperial Britain in South‐East Asia, Nicholas Tarling, Oxford University Press, Singapore, 1993, pages ix + 229, endpaper map, £20.00 hb. MODEL AND YARDSTICK Ghana: Part I, 1941–1952; Part II, 1952–1957, Richard Rathbone (editor), HMSO for the Institute of Commonwealth Studies, London, 1992, 2 vols, £60.00 each.

No abstract is provided for this article.

In Damaraland mole-rats (Fukomys damarensis), non-breeding subordinates contribute to the care of offspring born to the breeding pair in their group by carrying and retrieving young to the nest. In social mole-rats and some cooperative breeders, dominant females show unusually high testosterone levels and it has been suggested that high testosterone levels may increase reproductive and aggressive behavior and reduce investment in allo-parental and parental care, generating age and state-dependent variation in behavior. Here we show that, in Damaraland mole-rats, allo-parental care in males and females is unaffected by experimental increases in testosterone levels. Pup carrying decreases with age of the non-breeding helper while the change in social status from non-breeder to breeder has contrasting effects in the two sexes. Female breeders were more likely than female non-breeders to carry pups but male breeders were less likely to carry pups than male non-breeders, increasing the sex bias in parental care compared to allo-parental care. Our results indicate that testosterone is unlikely to be an important regulator of allo-parental care in mole-rats.

Multidrug-resistant Plasmodium falciparum malaria is a severe public health problem on the Thailand–Myanmar border. Many villagers buy packets of 4–5 mixed medicines (“yaa chud”) from shops without medical assessment as their first-line malaria treatment. In 2000–2001 a local researcher purchased 50 yaa chud from 44 shops around Mae Sot, Thailand and Myawaddy, Myanmar (Burma), for his wife who was said to be pregnant with fever and drowsiness. The tablets/capsules were provisionally identified by appearance and active ingredients determined in a subset by using mass and atomic spectrometry. The most frequently detected active ingredients were acetaminophen (22%), chlorpheniramine (13.4%), chloroquine (12.6%), tetracycline/doxycycline (11.4%), and quinine (5.1%). Only seven bags contained potentially curative medicine for malaria. A total of 82% of the bags contained medicines contraindicated in pregnancy. Inappropriate, ineffective antimalarial drugs on the Thailand–Myanmar border are likely to increase malaria morbidity, mortality and health costs and engender the emergence and spread of antimalarial drug resistance.

The efficacy of the traditionally recommended ampicillin (Amp) plus gentamicin (GM) regimen was compared with that of a trimethoprim-sulfamethoxazole (TMP/SMZ)-plus-GM regimen and the adequacy of 14 days total therapy for acute uncomplicated pyelonephritis (AUPN). Eighty-five women hospitalized for AUPN were randomly assigned to receive either Amp, 1 g intravenously (iv) every 6 h for 3 days, then 500 mg orally four times daily, or TMP/SMZ, 160/800 mg iv every 12 h for 3 days, then 160/800 mg orally twice daily. Initially, all patients also received GM every 8 h iv (mean, 6.6 doses). Antimicrobial resistance necessitated modifying therapy of 14(32%) of the Amp recipients but of none of the TMP/SMZ recipients (P < .001). Both regimens produced a satisfactory bacteriologic and clinical response in all cases. Reinfection occurred in 11% ofAmp and in 8% ofTMP/SMZ recipients. Nopatient experienced relapsing infection. The TMP/SMZ regimen was less costly and less likely to require modification due to antimicrobial resistance.

A case-control study was conducted to investigate the dietary and socio-economic factors associated with beriberi in infants attending three public hospitals in Vientiane, Lao PDR. Forty-three breast-feeding infants with a median (range) age of 3 (1-9) months were admitted with beriberi. This was defined as the presence of signs of congestive heart failure or shock in the absence of fever or other signs of sepsis, hypovolaemia or cardiac abnormalities, with rapid clinical improvement following parenteral thiamine. Subjects were matched by age and diet to 43 breast-feeding healthy control infants. Compared with control mothers, mothers of infants with beriberi had significantly less diet diversity (p <0.001), soaked glutinous rice for significantly longer or were more likely to pour off excess water from non-glutinous rice (p =0.006), had fewer years of schooling (p <0.05), were more likely to report that income was inadequate for basic needs (p <0.001), to perform hard physical labour (p <0.01) and to be married to farmers (p <0.01). Clinically significant thiamine deficiency in breastfed infants in Lao relates to methods of preparing rice, the food selected by lactating mothers and the family's socio-economic status.

No abstract is provided for this article.

The differentiation of malaria from other causes of fever in the absence of microscopy is notoriously difficult. Clinical predictors of malaria have been studied in an area of low and unstable transmission on the western border of Thailand. In 1527 children aged 2–15 years who were followed prospectively for 7 months, 82% (1254) had at least one febrile episode. Malaria caused 24% (301) of the first febrile episodes (Plasmodium falciparum 128, P. vivax 151, P. malariae 1, mixed infections with P. falciparum and P. vivax 21). Each malaria case was matched with the next child of similar age presenting to the dispensary with another cause of fever. Clinical symptoms or signs associated with a final diagnosis of malaria were: confirmed fever (≥38 °C) (odds ratio [OR] 1·6, 95% confidence interval [95% CI] 1·4–1·9), headache (OR 1·5, 95% CI 1·3–1·9), muscle and/or joint pain (OR 2·0, 95% CI 1·6–2·8), nausea (OR 1·7, 95% CI 1·4–2·3), clinical anaemia (OR 1·4, 95% CI 1·3–3·3), palpable spleen (OR 1·3, 95% CI 1·1–1·7), palpable liver (OR 1·4, 95% CI 1·1–2·1), absence of cough (OR 1·6, 95% CI 1·4–2·0), and absence of diarrhoea (OR 1·5,95% CI 1·2–2·4). None of these signs alone or in combination proved a good predictor of malaria. The best diagnostic algorithms (history of fever and headache without cough, and history of fever with an oral temperature ≥38 °C [sensitivity 51% for both, specificity 72 and 71%, respectively]) would result in prescription of antimalarial drugs in 28–29% of the non-malaria febrile episodes, and only 49% of the true malaria cases. Thus half of the potentially life-threatening P. falciparum infections would not be treated. Although multivariate analysis identified vomiting, confirmed fever, splenomegaly and hepatomegaly as independent risk factors for a diagnosis of falciparum malaria, use of these signs to differentiate falciparum from vivax malaria, and thus to determine antimalarial treatment, was insufficiently sensitive or specific. Malaria diagnosis should be confirmed by microscopical examination of a blood slide or the use of specific dipstick tests in areas of low transmission where highly drug-resistant P. falciparum coexists with P. vivax.

There are an estimated 150 million episodes of childhood pneumonia per year, with 11-20 million hospital admissions and 1.575 million deaths. Refugee children are particularly vulnerable, with poorly defined pneumonia epidemiology.We followed a birth cohort of 955 refugee infants, born over a one-year period, until two years of age. Clinical and radiographic pneumonia were diagnosed according to WHO criteria. Detailed characteristics were collected to determine risk factors for clinical, radiological and multiple episodes of pneumonia. Investigations were taken during a pneumonia episode to help determine or to infer an aetiological diagnosis.The incidence of clinical pneumonia was 0.73 (95% CI 0.70-0.75) episodes per child year (/CY) and of radiological primary endpoint pneumonia (PEP) was 0.22/CY (95% CI 0.20-0.24). The incidence of pneumonia without severe signs was 0.50/CY (95% CI 0.48-0.53), severe pneumonia 0.15/CY (95% CI 0.13-0.17) and very severe pneumonia 0.06/CY (0.05-0.07). Virus was detected, from a nasopharyngeal aspirate, in 61.3% of episodes. A reduced volume of living space per person (IRR 0.99, 95% CI 0.99-1.0, p = 0.003) and young maternal age (IRR 1.59, 95% CI 1.12-2.27, p = 0.01) were risk factors for developing pneumonia. The risk of a child having >1 episode of pneumonia was increased by having a shorter distance to the next house (IRR 0.86, 95% CI 0.74-1.00, p = 0.04). Infants were at risk of having an episode of PEP if there was a shorter distance from stove to bed (IRR 0.89, 95% CI 0.80-0.99, p = 0.03). Raised CRP and neutrophil values were associated with PEP.There was a high incidence of pneumonia in young children in this SE Asian refugee population. Viral infections were important, however CXR and non-specific marker findings suggested that bacteria may be involved in up to a third of cases.

1. Hypoglycaemia is a serious complication of falciparum malaria, especially in pregnant patients. To investigate malaria-associated changes in glucose metabolism in pregnancy, steady-state [6,6-2H2] glucose turnover and clearance were measured in 10 women (eight with uncomplicated falciparum malaria and two with vivax malaria at 16–30 weeks gestation) before treatment, after intravenous quinine infusion (patients with falciparum malaria) and in convalescence. 2. Admission basal plasma glucose concentrations were higher than those in convalescence [median (range); 4.8 (3.6-7.0) versus 4.0 (3.6-4.6) mmol/l, P = 0.02], and there was a significant fall during initial quinine treatment in patients with falciparum malaria [5.0 (4.3-7.6) to 3.6 (3.2-5.4) mmol/l, P &amp;lt;0.01]. Basal plasma insulin levels were comparable at presentation and follow-up (P = 0.35) and rose an average of only 2 m-units/l during quinine infusion (P &amp;lt;0.05). Pretreatment glucose turnover rates [3.37 (2.57-4.16) mgmin−1 kg−1] were comparable with those found in a previously reported study of non-pregnant severely ill patients [3.22 (2.12-4.82) mg min−1 kg−1, n = 11] and correlated significantly with the admission parasitaemia (P &amp;lt;0.025). In the eight patients with falciparum malaria, there was a significant fall in turnover during intravenous quinine infusion [3.42 (238-4.16) to 2.66 [1.94-3.94) mgmin−1 kg−1] whereas clearance did not change significantly. In convalescence, turnover values showed a wide scatter, although the highest values (3.34-4.33 mgmin−1 kg−1) were in patients studied within 4 days of presentation (two patients) or with pre-eclampsia (one patient); values for glucose clearance were consistently higher than those at presentation (P = 0.004). 3. Given the simultaneous plasma glucose and insulin concentrations, these results suggest that the combination of pregnancy and severe malaria may result in greater initial glucose requirements than in severely ill but non-pregnant patients, that there is a largely insulin-independent reduction in glucose production and utilization during quinine therapy which may partly reflect attenuated parasite glycolysis, and that early convalescence in pregnant women may be associated with higher glucose utilization than that in non-pregnant patients.