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.

'Smear-negative' pulmonary tuberculosis in a DOTS programme: poor outcomes in an area of high HIV seroprevalence.

SETTING: Lilongwe Central Hospital, Malawi. OBJECTIVES: To investigate 1) treatment outcome of a cohort of smear-negative pulmonary TB (snPTB) patients in an area of high human immunodeficiency virus (HIV) seroprevalence, and 2) whether poor treatment outcomes are due to non-TB patients being mistakenly treated for TB due to lack of diagnostic facilities. DESIGN: Patients about to be registered for snPTB treatment by the National TB Programme underwent further assessment including TB culture, bronchoscopy and bronchoalveolar lavage. All patients were followed up for 8 months. Standard TB control treatment outcomes were recorded. RESULTS: Of 352 snPTB patients assessed, 137 patients had bacteriologically confirmed TB, 136 had possible TB, and 79 had other non-TB diagnoses. The HIV seroprevalence rate was 89%. Outcomes were known for 325 (92%) patients: 129 (40%) died within 8 months. Death rates on TB treatment were 31% for bacteriologically confirmed TB patients and 35% for patients with possible TB but no bacteriological diagnosis. The death rate among patients with non-TB diagnoses was 53%. HIV infection significantly increased the risk of death (OR 3.9; P = 0.01). CONCLUSION: SnPTB is strongly associated with HIV infection in Malawi, where patients treated for snPTB have a poor prognosis. The high mortality is not fully explained by non-TB patients being mistakenly treated for TB.

Psychosocial risk factors for coronary disease in White, South Asian and Afro-Caribbean civil servants: the Whitehall II study.

BACKGROUND: Psychosocial factors are associated with the etiology and prognosis of coronary heart disease (CHD) in White populations; however, previous studies have not examined the distribution of psychosocial factors in ethnic groups with coronary rates higher (South Asian) and lower (Afro-Caribbean) than those of Whites. STUDY OBJECTIVE: To determine whether ethnic differences in psychosocial risk factors parallel those in CHD mortality. DESIGN: Cross-sectional survey. SETTING: 20 civil service departments in London. PARTICIPANTS: 8973 White, 577 South Asian, and 360 Afro-Caribbean office-based civil servants, aged 35-55 years. OUTCOME MEASURES: Minor psychiatric morbidity (General Health Questionnaire), social supports (marital status, social networks, negative aspects of support, confiding/emotional support, social support at work), psychosocial work characteristics (job control, effort-reward imbalance), hostility levels and presence of Type A personality. RESULTS: South Asians, compared to Whites, had more depression, higher negative supports, less social support at work, less job control, more effort-reward imbalance and higher levels of hostility, when adjusting for age and sex. Afro-Caribbeans, compared to Whites, had lower minor psychiatric morbidity and lower Type A scores. The remaining psychosocial factors showed either no ethnic differences in distribution, or differences contrary to those predicted from coronary event rates. Adjustment for employment grade made little difference to these associations. CONCLUSION: Among South Asians, the majority of whom were Indian, the distribution of psychosocial factors was consistent with ethnic differences in coronary rates; the pattern for Afro-Caribbeans was less consistent. Further research is required to test the extent to which psychosocial factors predict coronary events within ethnic groups and to characterize better psychosocial measures.

Investigating eosinophilia in patients returned from the tropics.

In patients who have returned from the tropics, eosinophilia usually signifies infection with worms. This paper gives an approach to investigating these patients systematically. The key element is a good travel history leading to targeted investigations.

Risk factors for human brucellosis in Yemen: a case control study.

Brucellosis is known to occur in Yemen but its epidemiology has not been extensively studied. The present investigation examined risk factors for human brucellosis in Yemen using a hospital-based case-control study. A total of 235 consecutive patients with brucellosis attending the Central Health Laboratory in Sana'a, Yemen, were matched in respect of age, sex, and place of residence, rural or urban, with 234 controls selected from individuals attending the Central Health Laboratory for unrelated health problems. Clinical information on patients and controls was supplemented with occupational and socio-economic data obtained by interview of cases and controls using a standard questionnaire. After controlling for confounding factors significant risk factors for infection related to occupation as a farmer (OR 2.5 (95% CI 1.4-4.5, P < 0.0001)), shepherd (OR 7.8 (95% CI 1.0-61, P 0.05)) or microbiologist (OR 24.5 (95% CI 2.9-204, P 0.003)); and drinking fresh milk (OR 2.0 (95% CI 1.3-4.3, P 0.001)) and laban (OR 22.7 (95% CI 1.7-4.2 P < 0.0001)). Taking other milk products and offal were not risk factors. Socio-economic and educational factors were also independent risk factors. Occupational, food and socio-economic risk factors significantly confounded one another. Yemen shares some but not all of the risk factors of neighbouring countries. The interrelation between the various factors is complex and studying any one in isolation may give a false impression of its public health significance. Control through education of the population to minimize exposure to, and contact with, animals and their milk and milk products and to boil milk before drinking it or using it to make buttermilk, would be difficult as these would represent such fundamental changes to established patterns of behaviour of this society. Ideally there would be a campaign to control the infection by animal vaccination but the costs and logistic difficulty would be great. Presently there is a clear need for doctors in Yemen to be made aware of the frequency of this infection, the means available for clinical and laboratory diagnosis and effective treatment, while strategies to control the disease in Yemen are formulated and field tested.

Utility of history, examination and laboratory tests in screening those returning to Europe from the tropics for parasitic infection.

OBJECTIVES: To examine the utility of the different elements of screening expatriates and travellers returned from the tropics for parasitic disease (exposure history, symptoms, examination and laboratory tests). METHODS: In phase 1 (conducted prospectively 1990-91), 1029 asymptomatic returnees had a detailed questionnaire and interview on risk-behaviour, physical examination and laboratory tests. In phase 2 (1997-98), 510 consecutive patients referred for routine screening (276 symptomatic and 234 asymptomatic) were screened with laboratory tests. RESULTS: Exposure history did not correlate reliably with parasite burden. In phase 1 physical examination revealed 387 abnormalities, only three of which indicated parasitic disease. Schistosomal serology was positive in 11% (CI 9-13) of these asymptomatic cases including patients with light or no reported freshwater exposure. Stool microscopy was positive in 19% (CI 16-22) of cases not correlated with reported eating habits, and eosinophilia was present in 8% (CI 6-10). In phase 2 reported symptoms did not correlate with parasitic disease. Schistosomiasis was present in 15% (CI 13-24) of asymptomatic and 18% (CI 13-22) of symptomatic individuals (OR 1.2 P = 0.46); stool microscopy was positive in 14% of both symptomatic and asymptomatic patients, and eosinophilia in 9% of symptomatic and 6% of asymptomatic individuals. CONCLUSION: Potentially serious asymptomatic infection is common in travellers. Detailed exposure history, symptom history and physical examination added little to detecting cases. Stool microscopy, schistosomal serology and eosinophil count all had good yield. Filarial serology had low yield in patients without eosinophilia.

Mortality rates and recurrent rates of tuberculosis in patients with smear-negative pulmonary tuberculosis and tuberculous pleural effusion who have completed treatment.

SETTING: Queen Elizabeth Central Hospital, Blantyre, and Zomba Central Hospital, Zomba, Malawi. OBJECTIVE: To follow-up human immunodeficiency virus (HIV) seropositive and HIV-seronegative patients with smear-negative pulmonary tuberculosis (PTB) and pleural TB who had completed treatment with two different regimens in Blantyre and Zomba, and to assess rates of mortality and recurrent TB. DESIGN: Patients with smear-negative and pleural TB who had completed 8 months ambulatory treatment in Blantyre or 12 months standard treatment in Zomba and who were smear and culture negative for acid-fast bacilli at the completion of treatment were actively followed every 4 months for a total of 20 months. RESULTS: Of 248 patients, 150 with smear-negative PTB and 98 with pleural TB, who completed treatment and were enrolled, 205 (83%) were HIV-positive. At 20 months, 145 (58%) patients were alive, 85 (34%) had died and 18 (7%) had transferred out of the district. The mortality rate was 25.7 per 100 person-years, with increased rates strongly associated with HIV infection and age >45 years. Forty-nine patients developed recurrent TB. The recurrence rate of TB was 16.1 per 100 person-years, with increased rates strongly associated with HIV infection, having smear-negative PTB and having received 'standard treatment'. CONCLUSION: High rates of mortality and recurrent TB were found in patients with smear-negative PTB and pleural effusion during 20 months of follow-up. TB programmes in sub-Saharan Africa must consider appropriate interventions, such as co-trimoxazole and secondary isoniazid prophylaxis, to reduce these adverse outcomes.

High mortality rates in tuberculosis patients in Zomba Hospital, Malawi, during 32 months of follow-up.

There is little information about long-term follow-up in patients with smear-negative pulmonary tuberculosis (PTB) or extrapulmonary tuberculosis (EPTB) who have been treated under routine programme conditions in sub-Saharan Africa. A prospective study was carried out to determine outcome 32 months from start of treatment in an unselected cohort of 827 adults TB inpatients registered at Zomba Hospital, Malawi, in 1 July-31 December 1995. By 32 months, 351 (42%) patients had died. Death rates were 30% (95% confidence interval [95% CI] 25-35%) in 386 patients with smear-positive PTB, 60% (95% CI 53-67%) in 211 patients with smear-negative PTB and 47% (95% CI 40-54%) in 230 patients with EPTB. Of the 793 patients with concordant HIV test results 612 (77%) were HIV seropositive: 47% HIV-positive patients were dead by 32 months compared with 27% HIV-negative patients (adjusted hazard ratio [HR] 2.3; 95% CI 1.7-3.1, P < 0.001). Smear-negative PTB patients had the highest death rates during the 32-month follow-up (HR 2.7; 95% CI 2.1-3.5, P < 0.001 compared to smear-positive patients), followed by EPTB patients (HR 1.9; 95% CI 1.5-2.5, P < 0.001 compared to smear-positive patients). When analysis was restricted to after the treatment period had finished (i.e., months 12-32), the differences in mortality were maintained for HIV-serostatus and for types of TB. Low-cost, easy to implement strategies for reducing mortality in HIV-positive TB patients in sub-Saharan Africa (such as the use of trimethoprim-sulphamethoxazole prophylaxis) need to be tested urgently in programme settings.

Urban/rural differences in prevalence and risk factors for intestinal helminth infection in southern Malawi.

Urbanization may increase the risk of human infection with intestinal helminths. A cross-sectional survey was conducted to investigate the prevalence, intensity and potential risk factors of acquiring such infection, among children aged 3-14 years in similar urban and rural communities in southern Malawi. Stool samples were collected from 553 children (273 urban and 280 rural). The overall prevalence of helminth infection was significantly higher in the urban subjects than in the rural (16.5% v. 3.6%; P < 0.001), mostly because of differences in the prevalence of Ascaris lumbricoides infection. Living in an urban community was associated with a significantly higher risk of infection [odds ratio (OR) = 5.3; 95% confidence interval (CI) = 2.6-12.1], even after controlling for potential confounding factors. In the urban community, risk factors included having pools of water/sewage around houses (OR = 3.0; CI = 1.4-6.5), not wearing shoes (OR = 7.1; CI = 2.7-19.2), not attending school (OR = 2.8; CI = 1.2-6.5), having mothers with 4-8 years of education (OR = 5.2; CI = 2.0-14.0), and having mothers below 35 years of age (OR = 4.09; CI = 1.39-16.28). In this part of Africa, efforts to reduce helminth infections may best be focused on reducing geohelminth burden in urban areas.