Do doctors under-provide, over-provide or do both? Exploring the quality of medical treatment in the Philippines.

OBJECTIVE: To assess the quality of medical treatment by disaggregating quality into components that distinguish between insufficient and unnecessary care. DESIGN: Randomly selected doctors were asked how they would treat a sick child. Their responses were disaggregated into how much of an evidence-based essential treatment plan was completed and the number of additional non-essential treatments that were given. Key variables included the expected cost, the health consequences of insufficient and unnecessary care and comparisons between public and private physicians. Responses to 160 clinical performance vignettes (CPVs) were analysed. SETTING: Philippines. PARTICIPANTS: One hundred and forty-three public and private physicians in the Philippines, collected in November 2003-December 2004 and September 2006-June 2007. INTERVENTIONS: CPVs administered to physicians. MAIN OUTCOME MEASURES: Process quality measures (accounting for the possibility of both over-treatment and under-treatment). RESULTS: Based on CPVs, doctors gave both insufficient and unnecessary treatment to under-five children in 69% of cases. Doctors who provided the least sufficient care were also the most likely to give costly or harmful unnecessary care. Insufficient care typically had potentially worse health consequences for the patient than unnecessary care, though unnecessary care remains a concern because of overuse of antibiotics (47%) and unnecessary hospitalization (34%). CONCLUSIONS: Quality of care is complex, but over- and under-treatment coexist and, in our analysis physicians that were more likely to under-treat a sick child were also those more likely to over-treat.

Estimating unreported malaria cases in England: a capture-recapture study.

A capture-recapture study was undertaken to estimate the incidence and likely total burden of malaria cases in England. Cases diagnosed by the national Malaria Reference Laboratory (MRL) between July 2003 and December 2004 were matched with cases reported to Hospital Episode Statistics using demographic, geographical, parasitological, and temporal information. A total of 3861 cases were recorded in one or both datasets; the 'unknown population' was estimated as 746 cases (95% CI 677-822) giving a total of 4607 cases (95% CI 4446-4767) over 18 months. Eighty-four percent (95% CI 83-85) of cases were recorded in one or both datasets. Fifty-six percent (95% CI 54-58) of cases were captured by the MRL surveillance system; ascertainment for Plasmodium falciparum and London cases was higher at 66% and 62%, respectively. Improving case ascertainment will facilitate effective measures to reduce the burden of this preventable disease in the UK.

Falciparum malaria as a cause of fever in adult travellers returning to the United Kingdom: observational study of risk by geographical area.

BACKGROUND: The probability that a returned traveller with a history of fever has malaria is likely to vary by geographical area, but this has not been quantified in travellers. AIM: To collect data on prevalence of malaria in outpatients returning with a fever or history of fever from malaria-endemic countries, at the point of presentation for a malaria test. DESIGN: Observational retrospective study. Consecutive patients presenting to an unselected 'walk-in' clinic for returned travellers. RESULTS: Of 2867 patients meeting inclusion criteria, 337 (11.8%) had malaria, 89.5% originating in sub-Saharan Africa. Of travellers returning from sub-Saharan Africa excluding South Africa with fever/history of fever, 291/1497 had malaria (19.4%, 95% CI 17-21%). A high proportion was visiting friends and relatives. In those from other areas the proportions were: 16/707 (2.3%, 95% CI 1.5-3.8) from Indian subcontinent/Southeast Asia; 2/143 (1.4%) from Southern America; 4/129 (3.1%) from South Africa; 1/44 (2.3%) from North Africa; and 8/41 (19.5%) from Oceania. Compared to other malaria-endemic regions, African travel gave an adjusted odds ratio of 7.8 (95% CI 5.4-11.2, P < 0.0001). Only 45.1% of malaria cases had a fever (> or =37.5 degrees C) at the time of presentation. Only 3% of all diagnoses of malaria had no history of fever. In 28% of cases parasite count increased in the initial 24 h of antimalarial treatment. CONCLUSION: The likelihood that a patient with fever returning from Africa has malaria is high (around 1 in 5), and is significantly lower from other areas. Absence of fever at presentation does not exclude malaria.

Amodiaquine and artemether-lumefantrine select distinct alleles of the Plasmodium falciparum mdr1 gene in Tanzanian children treated for uncomplicated malaria.

The artemisinin-based combination therapies artemether-lumefantrine (AL) and amodiaquine (AQ) plus artesunate have been adopted for treatment of Plasmodium falciparum malaria in many African countries. Molecular markers of parasite resistance suitable for surveillance have not been established for any of the component drugs in either of these combinations. We assessed P. falciparum mdr1 (Pfmdr1) alleles present in 300 Tanzanian children presenting with uncomplicated falciparum malaria, who were enrolled in a clinical trial of antimalarial therapy. Pfmdr1 genotype analysis was also performed with isolates from 182 children who failed AQ monotherapy and 54 children who failed AL treatment. Pfmdr1 alleles 86Y, 184Y, and 1246Y were more common among treatment failures in the AQ group than among pretreatment infections. The converse was found in the AL-treated group. Children presenting with the 86Y/184Y/1246Y Pfmdr1 haplotype and treated with AQ were significantly more likely to retain this haplotype if they were parasite positive during posttreatment follow-up than were children treated with AL (odds ratio, 33.25; 95% confidence interval, 4.17 to 1441; P, <0.001). We conclude that AL and AQ exert opposite within-host selective effects on the Pfmdr1 gene of P. falciparum.

Cost-Effectiveness Study of Three Antimalarial Drug Combinations in Tanzania

Background: As a result of rising levels of drug resistance to conventional monotherapy; the World Health Organization (WHO) and other international organisations have recommended that malaria endemic countries move to combination therapy; ideally with artemisinin-based combinations (ACTs). Cost is a major barrier to deployment. There is little evidence from field trials on the cost-effectiveness of these new combinations. Methods and Findings: An economic evaluation of drug combinations was designed around a randomised effectiveness trial of combinations recommended by the WHO; used to treat Tanzanian children with non-severe slide-proven malaria. Drug combinations were: amodiaquine (AQ); AQ with sulfadoxine-pyrimethamine (AQ+SP); AQ with artesunate (AQ+AS); and artemether-lumefantrine (AL) in a six-dose regimen. Effectiveness was measured in terms of resource savings and cases of malaria averted (based on parasitological failure rates at days 14 and 28). All costs to providers and to patients and their families were estimated and uncertain variables were subjected to univariate sensitivity analysis. Incremental analysis comparing each combination to monotherapy (AQ) revealed that from a societal perspective AL was most cost-effective at day 14. At day 28 the difference between AL and AQ+AS was negligible; both resulted in a gross savings of approximately US$1.70 or a net saving of US$22.40 per case averted. Varying the accuracy of diagnosis and the subsistence wage rate used to value unpaid work had a significant effect on the number of cases averted and on programme costs; respectively; but this did not change the finding that AL and AQ+AS dominate monotherapy.Conclusions: In an area of high drug resistance; there is evidence that AL and AQ+AS are the most cost-effective drugs despite being the most expensive; because they are significantly more effective than other options and therefore reduce the need for further treatment. This is not necessarily the case in parts of Africa where recrudescence following SP and AQ treatment (and their combination) is lower so that the relative advantage of ACTs is smaller; or where diagnostic services are not accurate and as a result much of the drug goes to those who do not have malaria

Serological speciation of human schistosome infections by ELISA with a panel of three antigens.

AIMS: To find out whether serology can reliably speciate human schistosomiasis using a simple enzyme linked immunosorbent assay (ELISA) technique. METHODS: Stored sera from 66 patients with microscopically confirmed schistosomiasis were subjected to ELISA using a panel of three antigens, namely: unfractionated Schistosoma mansoni soluble egg antigen (SEA); CEF6, a cationic fraction of SEA; and crude S margrebowiei egg antigen, prepared from an animal schistosome closely related to S haematobium. RESULTS: The optical densities (ODs) obtained using CEF6 as antigen were significantly higher in sera from S mansoni infected patients than in sera from S haematobium infected patients (median OD, 0.810 v 0.595). Using S margrebowiei egg antigen, the optical densities were significantly higher in S haematobium sera than in S mansoni sera (median OD, 0.794 v 0.544). There was no significant difference in optical densities between S mansoni and S haematobium sera using SEA (median OD, 0.725 v 0.737). The ratio of ODs (CEF6 to S margrebowiei egg antigen) was calculated: a ratio of >1 indicated S mansoni infection (sensitivity, 88%) and a ratio of <1 indicated S haematobium infection (sensitivity, 84%). The odds ratio for S haematobium having an OD ratio of <1 was 36.8 (95% confidence interval, 7.0 to 194). CONCLUSIONS: The identity of the infecting species of schistosome can be determined using the panel of antigens described. SEA should be used to screen serum samples, and the CEF6 : S margrebowiei egg antigen ELISA optical density ratio can be used where serological speciation is required.

Falciparum malaria in malaria-naive travellers and African visitors.

BACKGROUND: Patients from malaria-endemic areas who present in non-endemic countries with Plasmodium falciparum malaria are often assumed to have some degree of immunity. If this were reliably true, it would simplify their management. AIM: To determine whether being born and resident in a malaria-endemic country is a predictor of clinical course in UK admissions for malaria. DESIGN: Prospective observational study. METHODS: We compared clinical and laboratory parameters between two groups of adult patients with acute P. falciparum malaria, admitted to the Hospital for Tropical Diseases in London: one born and resident in non-endemic countries (n=167); the other born and resident in malaria-endemic countries of Africa (n=93). Patients were excluded if they had taken prophylaxis or prior treatment. RESULTS: There were no differences between these two groups in terms of peak parasitaemia or time to parasite clearance. There was a significantly higher risk of malaria-naive patients having peak parasitaemia >5% (OR 4.5, 95%CI 1.5-13.2). Of those usually resident in Africa, 31% required parenteral treatment compared to 41% of the malaria-naive group. Of the visitors from Africa, 4.3% needed admission to the Intensive Therapy Unit (ITU), although there was a tendency for more malaria-naive patients to require ITU care (OR 2.69, 95%CI 0.9-8.1). DISCUSSION: While there are differences in presentation between those who are malaria-naive and those who live in malaria-endemic African countries, making assumptions about the immunity or clinical course of an individual patient with malaria presenting in the UK on the basis of presumed history of exposure is unwise.

Investigation of tropical eosinophilia; assessing a strategy based on geographical area.

OBJECTIVES: Patients with eosinophilia are an important clinical problem. This study aimed to assess the most efficient manner of investigating patients with peripheral eosinophilia (eosinophil count >0.5x10(9)ml(-1)) presenting from the tropics. METHODS: Patients attending the Hospital for Tropical Diseases, London, from October 1997 to March 2002 for investigation of eosinophilia were identified prospectively. Laboratory, clinical and demographic data were recorded from laboratory and clinical records. An investigation set was proposed prospectively and assessed for all geographical areas (stool microscopy, strongyloides culture and serology), all of Africa (additional schistosomal serology, terminal urine microscopy and filarial serology) and West Africa (additional day-bloods for microfilaria). RESULTS: Data was analysed for 261 patients. At least one helminthic cause for eosinophilia was found in 64% of patients (median eosinophilia 1.2x10(9)ml(-1)). Seventeen per cent of patients had more than one helminth species found. Median eosinophilia increased with number of diagnoses per patient. The proposed investigation sets were validated, with high yield for all proposed tests apart from filarial serology outside West Africa, and good sensitivity. CONCLUSIONS: Initial investigation of eosinophilia in patients presenting from the tropics may be guided by a simple investigation set depending on broad area of travel which has high sensitivity and yield. Patients frequently have more than one helminthic cause of eosinophilia.

Are intestinal helminths a risk factor for non-typhoidal Salmonella bacteraemia in adults in Africa who are seropositive for HIV? A case-control study.

In Africa, invasive, non-typhoidal Salmonella (NTS) infections are a common but life-threatening complication in adults who are seropositive for HIV. The high prevalence of human infection with intestinal helminths which penetrate the gut could explain the greater importance of NTS bacteraemia in Africa compared with that in industrialized countries. If helminth infection is a major risk factor for NTS it would provide a locally relevant, public-health target. Intestinal helminth carriage in 57 HIV-positive patients with NTS bacteraemia (the cases) was compared with that in 162 HIV-positive controls who were similar to the cases in terms of age, sex, urban dwelling and socio-economic factors. The prevalence of helminth infection, 29% overall, was lower among the cases (18%) than among the controls (33%), giving a crude odds ratio of 0.40 [with a 95% confidence interval (CI) of 0.21-0.9] and an adjusted odds ratio (aOR) of 0.79 (CI = 0.4-1.8). Five (9%) of the cases and 12 (7%) of the controls were infected with nematodes which penetrate the gut (Ascaris lumbricoides and/or Strongyloides stercoralis). The aOR for infection with these penetrating worms, corrected for age, sex, urban dwelling and phase of study, was 1.40 (CI = 0.4-4.5). The present results do not exclude the possibility that helminths play a role in invasive NTS infections, but are not consistent with helminths being a sufficient risk factor in this population to be a public-health target. Anthelmintics are unlikely to have a major impact on preventing NTS bacteraemia in patients diagnosed HIV-positive in Africa.