Purchase of antibiotics without prescription in Manila, the Philippines. Inappropriate choices and doses.

The purchase of antimicrobial agents in drugstores in a district in Manila. The Philippines was examined in order to determine how these agents might be used. Most antimicrobial agents are imported as bulk products and repackaged by a large number of small firms into 1491 different preparations including 206 marketed as combinations with other drugs. Antimicrobial agents accounted for 20.1% of all drug purchases. Purchases were made without prescription in 66.3% of 1608 transactions. Most of these were aminopenicillins or penicillins G or V (40.0%). The most common perceived indications were respiratory tract infections (20.2%), tuberculosis (8.8%), "prophylaxis" (8.6%) and gastrointestinal infection (8.3%). Almost 90% of purchases were for 10 or less capsules or tablets. The median number of units purchased was 3. Customers with written prescriptions purchased a mean of 8 while those who self-prescribed purchased a mean of 4 units (p = less than 0.05). We believe that these practices can provide only limited clinical efficacy and should favor emergence of resistant bacteria.

A cost-effectiveness analysis of a simple micromethod for hepatitis B screening in hepatitis B virus control programmes.

We developed a simple micromethod for identifying mothers who are most likely to transmit hepatitis B infection to their infants, using reverse passive haemagglutination for detecting HBsAg (hepatitis B surface antigen) in capillary blood. This screening method was evaluated against other strategies for hepatitis B control by means of decision- and cost-effectiveness analyses. The micromethod was shown to be cost-effective when the cost of hepatitis B vaccine was high. However, with increasingly reduced costs of the vaccine, it may have a limited role in a programme of mass immunization for hepatitis B.

The role of clinical epidemiology in establishing essential national health research capabilities in developing countries.

Health research directly relevant to the needs of the people of developing countries is essential for equity in development as well as for improving health planning and management. the international Commission on Health Research for Development has stressed the need to strengthen the capacity of developing countries, no matter how poor, to carry out essential national health research (ENHR). Clinical epidemiologists in developing countries can significantly contribute to the manpower available for ENHR. They play a major role in the provision and practice of appropriate health care by contributing to the critical assessment of priority health problems and by carrying out scientific evaluation of new and conventional intervention tools. In clinical epidemiology units in developing countries, transdisciplinary collaboration with social scientists and health economics has enhanced the capacity to do research that would influence decision-making and health policy, even as links with ministries of health and other ENHR-committed networks are being strengthened. The potential for carrying out ENHR will be multiplied as national and regional training centers for clinical epidemiology in selected developing countries are established.

Institutional linkages: strategic bridges for research capacity strengthening.

The establishment and strengthening of research capacity in developing countries is of prime importance in empowering these countries to find rational and efficient solutions to their health problems through scientific research. Institutional linkages with other researchers in the North and South greatly facilitate the process of research strengthening through graduate study programs, technology transfer, 'hands-on' research training in the field, expanded networking with partners' contacts, and continued scientific exchanges in the context of actual research programs. This paper describes the experiences of the Research Institute for Tropical Medicine, the Philippines, in the area of research capacity development. Strengths and weaknesses of various approaches in institutional strengthening are discussed.

Risk factors for infection with malaria in a low endemic community in Bataan, the Philippines.

The patterns of malaria morbidity and mortality can vary with the level of malaria transmission in a given area. We carried out two annual cross-sectional surveys in the hypoendemic malarious community of Morong, the Philippines, to examine epidemiologic and sociobehavioural risk factors for infection. In both surveys, the greatest risk of having malaria was associated with place of residence. For example, in the first survey, living in an area where more than 50% of the community had a high IFAT titer had an adjusted odds ratio (OR) of 33.7. A range of activities thought to be associated with risk were examined, but in the first survey, only frequent nocturnal visits to the forest were found to be a significant risk factor overall (adjusted OR; 2.65; 95% CI 1.48, 4.73), but this phenomenon was primarily observed among individuals residing in the lowest prevalence areas. In the second survey, where only the area with a relatively high prevalence of malaria was sampled, no association with activities was found. In this survey, significant factors associated with malarial infection were: being a migrant (adjusted OR 1.97; 95% CI 1.33, 2.92), being male (adjusted OR 1.63; 95% CI 1.10, 2.43) and age 30 years or less (adjusted OR 0.29 for age > 30 years; 95% CI 0.16, 0.52). The data suggest that in low-endemic communities like Morong, Bataan, control efforts should be primarily directed to focal areas identified by serology, particularly among migrants and among male young adults.

Field epidemiological studies on malaria in a low endemic area in the Philippines.

Field epidemiological studies were conducted to examine factors affecting endemicity in an area with a low prevalence of malaria. Two annual cross sectional surveys were done to estimate parasite prevalence rates at two periods in time, to determine the distribution of the parasitemic population and to describe the serological status of the population. A longitudinal study of a sample of infected people was used to measure reinfection rates and antibody dynamics. A 2 year passive case detection was done to estimate the number and distribution of people with symptomatic infections. Malaria was found in all age groups, with marked clustering of cases. Active and passive case detection and serological surveys all gave a similar pattern of malaria distribution: generally low prevalence with small foci of relatively high endemicity. The infection frequencies were generally similar in all age groups, measured by both active and passive case detection. There was a high frequency of P. falciparum gametocytemic infections in the asymptomatic cases found through active case detection. Twenty to 39 year old males had the highest frequency of infection by active case detection, and 10-19 year old males by passive case detection. These two groups were also more likely to be gametocyte positive than their female counterparts, suggesting that in this community, this portion of the population acts as the main reservoir of infection.

Stability of malaria in a community in Bataan, the Philippines: prospects for control.

Malaria in Morong, Bataan, The Philippines, a municipality with relatively low level, but stable malaria is associated with small foci of relatively high endemicity. Although there is little association between age and symptomatic malaria, there is a reservoir of asymptomatic cases which are present throughout the year. Risk analysis suggests that the greatest risk factor in acquiring malaria depends on place of residence and not on occupation, including those associated with forest activities such as charcoal making. Foci of infection and the timing of symptomatic cases is closely correlated with breeding sites and abundance of adult Anopheles flavirostris. In spite of this close association, widely held views in the community that malaria is not related to mosquito transmission are likely to make better malaria control based on vector control difficult to sustain. Observation of treatment practices in the community and estimates of the number of apparently asymptomatic carriers from active case detection illustrate the importance of delayed treatment in providing a continuing reservoir of infection. These results highlight the need for improved early case detection and treatment.

Local knowledge and treatment of malaria in Agusan del Sur, The Philippines.

Information about local knowledge of malaria, its transmission, treatment and prevention were gathered at the outset of a Malaria Control Program in order to incorporate this information into community interventions. Data were collected using focus groups and indepth interviews with caretakers of children who had had a recent episode of malaria. These were supplemented as baseline data through a survey and the ongoing participation of researchers in the intervention. Local knowledge of malaria was influenced by clinical diagnosis and was based on the coexistence of signs of illness. People conventionally self-medicated or used herbs for symptomatic relief prior to seeking clinical diagnosis and treatment, with treatment delay influenced by the logistic difficulties within the region, direct and indirect costs associated with treatment seeking, and delays in the return of results once a blood film for diagnosis was made. People were familiar with mosquito control activities conducted by the Malaria Control Service and, as a result, most respondents associated malaria with mosquitos. However, the role of the mosquito as the sole vector, and the means by which malaria was transmitted, were not well appreciated.

Intravenous immunoglobulin for treating sepsis and septic shock.

BACKGROUND: Death from severe sepsis and septic shock is common, and researchers have explored whether antibodies to the endotoxins in some bacteria reduces mortality. OBJECTIVES: To estimate the effects of intravenous immunoglobulin (IVIG) in patients with bacterial sepsis or septic shock on mortality, bacteriological failure rates, and duration of stay in hospital. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group specialized register up to November 2001; the Cochrane Controlled Trials Register, The Cochrane Library issue 4, 2001; MEDLINE 1966 to November 2001; and EMBASE 1988 to September 2001. We contacted investigators active in the field for unpublished data. SELECTION CRITERIA: Randomised trials comparing intravenous immunoglobulin (monoclonal or polyclonal) with placebo or no intervention, in patients with bacterial sepsis or septic shock. DATA COLLECTION AND ANALYSIS: Inclusion criteria, trial quality assessment, and data abstraction were done in duplicate. We conducted pre-specified subgroup analyses by type of immunoglobulin preparation. MAIN RESULTS: Twenty-seven out of 55 studies met our inclusion criteria. Pooled analysis of all types of IVIG preparations revealed a significant trend toward reduction of mortality (n= 8,856; RR=0.91; 95%CI 0.86-0.96). Overall mortality was reduced in patients who received polyclonal IVIG (n=492; RR=0.64; 95% CI 0.51 to 0.80). For the two high-quality trials on polyclonal IVIG, the RR for overall mortality was 0.30, but the confidence interval was wide (95% CI 0.09 to 0.99, n=91). Mortality was not reduced among patients who received monoclonal antibodies such as anti-endotoxins (n=2,826 in 5 good-quality studies; RR=0.97; 95% CI 0.88 to 1.07) or anti-cytokines (n=4,318; RR=0.93; 95% CI 0.86 to 1.01). A few studies measured secondary outcomes (deaths from sepsis or length of hospitalisation) but no differences in the intervention and control groups were identified except among those who received polyclonal IVIG, where sepsis-related mortality was significantly reduced (n=161; RR=0.35; 95% CI 0.18 to 0.69). REVIEWER'S CONCLUSIONS: Polyclonal IVIG significantly reduced mortality and and is a promising adjuvant in the treatment of sepsis and septic shock. However, all the trials were small and the totality of the evidence is insufficient to support a robust conclusion of benefit. Adjunctive therapy with monoclonal IVIGs remains experimental.

Intravenous immunoglobulin for treating sepsis and septic shock.

OBJECTIVES: Death from severe sepsis and septic shock is common, and researchers have explored whether antibodies to the endotoxins in some bacteria reduces mortality. This review summarises the effects of intravenous immunoglobulin (IVIG) in patients with bacterial sepsis or septic shock on mortality, bacteriological failure rates, and duration of stay in hospital. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, Medline 1966 to April 1999, EMBASE 1988 to February 1999; we contacted investigators active in the field for unpublished data. SELECTION CRITERIA: Randomised trials comparing intravenous immunoglobulin (monoclonal or polyclonal) with placebo or no intervention, in patients with bacterial sepsis or septic shock. DATA COLLECTION AND ANALYSIS: Inclusion criteria, trial quality assessment, and data abstraction were done in duplicate. We conducted pre-specified subgroup analyses by type of immunoglobulin preparation. MAIN RESULTS: Twenty-three out of 49 studies met our inclusion criteria. Overall mortality was reduced in patients who received polyclonal IVIG (n=413; RR=0.60; 95% CI 0.47 to 0.76). Mortality was not reduced among patients who received monoclonal antibodies such as anti-endotoxins (n=1,736 in 4 good-quality studies; RR=0.98; 95% CI 0.86 to 1.12) or anti-cytokines (n=4,318; RR=0.93; 95% CI 0.86 to 1.01). A few studies measured secondary outcomes (deaths from sepsis or length of hospitalisation) but no differences in the intervention and control groups were identified except among those who received polyclonal IVIG, where sepsis-related mortality was significantly reduced (n=161; RR=0.35; 95% CI 0.18 to 0.69). REVIEWER'S CONCLUSIONS: In our opinion, polyclonal IVIG significantly reduces mortality and can be used as an adjuvant treatment for sepsis and septic shock. Adjunctive therapy with monoclonal IVIGs remains experimental.

Intravenous immunoglobulin for treating sepsis and septic shock.

OBJECTIVES: Death from severe sepsis and septic shock is common, and researchers have explored whether antibodies to the endotoxins in some bacteria reduces mortality. This review summarises the effects of intravenous immunoglobulin (IVIG) in patients with bacterial sepsis or septic shock on mortality, bacteriological failure rates, and duration of stay in hospital. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, MEDLINE 1966 to 2000, EMBASE 1988 to February 1999; we contacted investigators active in the field for unpublished data. SELECTION CRITERIA: Randomised trials comparing intravenous immunoglobulin (monoclonal or polyclonal) with placebo or no intervention, in patients with bacterial sepsis or septic shock. DATA COLLECTION AND ANALYSIS: Inclusion criteria, trial quality assessment, and data abstraction were done in duplicate. We conducted pre-specified subgroup analyses by type of immunoglobulin preparation. MAIN RESULTS: Twenty-seven out of 55 studies met our inclusion criteria. Pooled analysis of all types of IVIG preparations revealed a significant trend toward reduction of mortality (n= 8,856; RR=0.91; 95% CI 0.86 to 0.96). Overall mortality was reduced in patients who received polyclonal IVIG (n=492; RR=0.64; 95% CI 0.51 to 0.80). Mortality was not reduced among patients who received monoclonal antibodies such as anti-endotoxins (n=2,826 in 5 good-quality studies; RR=0.97; 95% CI 0.88 to 1.07) or anti-cytokines (n=4,318 in 4 good quality studies; RR=0.93; 95% CI 0.86 to 1.01). A few studies measured secondary outcomes (deaths from sepsis or length of hospitalisation) but no differences in the intervention and control groups were identified except among those who received polyclonal IVIG, where sepsis-related mortality was significantly reduced (n=161; RR=0.35; 95% CI 0.18 to 0.69). REVIEWER'S CONCLUSIONS: In our opinion, polyclonal IVIG significantly reduces mortality and can be used as an adjuvant treatment for sepsis and septic shock. Adjunctive therapy with monoclonal IVIGs remains experimental.

Evaluation of a single Widal test in the diagnosis of enteric fever.

The usefulness of a single Widal test was evaluated in an endemic area. This test was done on 62 bacteriologically proven enteric fever cases, 69 non-enteric fever cases and healthy individuals. Using an 0 antibody cut-off of greater than or equal to 1:20, the Widal tube agglutination test yielded a sensitivity of 61% and a specificity of 88%. At a pre-test probability of around 50%, the positive predictive value was 83% and the negative predictive value was 72%. A 4% prevalence of 0 antibodies was noted in the healthy population.

Epidemiology and control of hepatitis B infection: a perspective from the Philippines, Asia.

The prevalence of chronic hepatitis B virus (HBV) infection in the Philippines, as indicated by hepatitis B surface antigen (HBsAg) positivity, ranges from 2% to 16.5%, with an average of 12% in a study of rural villagers. Although mother to child transmission is a major route of HBV infection, other routes (particularly child to child transmission) play an important part after the first year of life. In a study assessing the feasibility and effectiveness of incorporating hepatitis B vaccine into the national Expanded Programme on Immunisation, the coverage rate for fully immunised 1 year olds ranged from 80.9-84% and anti-HBs seroconversion rates ranged from 72-88%. In countries where HBV is not endemic, high risk groups include commercial sex workers (CSWs) and intravenous drug users (IVDUs), who generally have higher HBsAg positivity rates than the general population. In countries with a high HBV endemicity, carrier rates may be only slightly higher among CSWs, suggesting that other modes of transmission are more important in those regions. CSWs who are also IVDUs are at even greater risk. If HBV infection is to be controlled, innovative education and screening programmes are needed, together with the mass immunisation of neonates now started in many countries around the world.

Patterns of treatment for malaria in Tayabas, The Philippines: implications for control.

This paper describes local understandings of illness and documents treatment-seeking behaviour in Tayabas, Quezon, The Philippines. Data were collected using focus group discussions and narrative interviews with adults and with mothers of children, who had had confirmed malaria during a two-month surveillance period. Signs and symptoms of malaria are important in directing individual diagnosis, treatment-seeking and therapy. Household therapy with antimalarials, and more commonly antipyretics and herbs, as used before seeking care from either the formal or informal sector. Care outside the home was sought where symptoms continued and/or worsened, with an average period of time from onset of symptoms to presentation to a clinic of six days. Accessibility to clinics is not a problem in the study area and hence the primary reason for delay was propensity to self-treat first and to discontinue medication when feeling better. These factors affect the control of malaria and the potential to reduce transmission. Better advice to the community regarding the importance of diagnosis and compliance with antimalarial therapy is indicated.

Patterns of familial transmission of HBV and the risk of developing liver cancer: a case-control study in the Philippines.

The present case-control study was carried out in the Philippines to determine the risk of developing hepatocellular carcinoma (HCC) in relation to different HBV serological profiles of parents and sibs of HCC cases and controls. The HBV serological profiles of parents and sibs of 33 patients with HCC were compared with those of 2 types of community control: 33 general population controls matched for sex and age (C1 controls) and 33 asymptomatic HBsAg carriers also matched for sex and age (C2 controls). When cases were compared with C1 controls, increased risks were associated with the fact of having an HBsAg-positive mother (RR = 2.5, 95% C1 = 0.4-26.3) and older sibs positive for HBsAg (RR = 2.0, 95% C1 = 0.5-9.1), but the increased risk was not statistically significant. However, a significantly increased risk was associated with the fact of having a mother (95% C1 = 3.5-infinity) or father (RR = 11, 95% C1 = 1.6-473) who had been exposed to HBV. On the other hand, when cases were compared with C2 controls, a non-significant 2-fold increase was associated with the fact of having an HBsAg-positive mother, but no differences were observed in the HBV serological profiles of their fathers and older sibs. These results suggest that, in the Philippines, the fact of having a mother or father who has been infected in the past with HBV increases the risk of developing HCC but that the contribution of the mother to this increase in risk is not as important as hitherto believed.

Corticosteroid treatment for sepsis: a critical appraisal and meta-analysis of the literature.

OBJECTIVE: To determine the effect of corticosteroid therapy on morbidity and mortality in patients with sepsis. DATA SOURCES: We searched for published and unpublished research using MEDLINE, EMBASE, and the Science Citation Index, manual searching of Index Medicus, citation review of relevant primary and review articles, personal files, and contact with primary investigators. STUDY SELECTION: From a pool of 124 potentially relevant articles, duplicate independent review identified nine relevant, randomized, controlled trials of corticosteroid therapy in sepsis and septic shock among critically ill adults. DATA EXTRACTION: In duplicate, independently, we abstracted key data on population, intervention, outcome, and methodologic quality of the randomized controlled trials. DATA SYNTHESIS: Corticosteroids appear to increase mortality in patients with overwhelming infection (relative risk 1.13, 95% confidence interval 0.99 to 1.29), and have no beneficial effect in the subgroup of patients with septic shock (relative risk 1.07, 95% confidence interval 0.91 to 1.26). Studies with the highest methodologic quality scores also suggest a trend toward increased mortality overall (relative risk 1.10, 95% confidence interval 0.94 to 1.29). A similar trend was observed for patients with septic shock (relative risk 1.12, 95% confidence interval 0.95 to 1.32). No difference in secondary infection rates was demonstrated in corticosteroid-treated patients with sepsis or septic shock. However, there was a trend toward increased mortality from secondary infections in patients receiving corticosteroids (relative risk 1.70, 95% confidence interval 0.70 to 4.12). The occurrence rate of gastrointestinal bleeding was increased slightly in the treatment group (relative risk 1.17, 95% confidence interval 0.79 to 1.73). CONCLUSIONS: Current evidence provides no support for the use of corticosteroids in patients with sepsis or septic shock, and suggests that their use may be harmful. These trials underscore the need for future methodologically rigorous trials evaluating new immune-modulating therapies in well-defined critically ill patients with overwhelming infection.

Mother to child transmission of hepatitis B virus in the Philippines.

A follow-up study of mother to infant transmission of hepatitis B virus was conducted in the Philippines between 1981 and 1983. The prevalence of HBsAg among 527 mothers was 8.5%. Overall, seven out of 17 (41.2%) infants born to HBsAg carrier mothers became HBsAg positive within the first 12 months of life. The risk of becoming HBsAg positive was about 20 times higher for infants born to HBsAg positive mothers than for infants born to HBsAg negative mothers (OR = 18.9, 95% Ci = 2.0-86.6). The risk was even higher if the mother was a carrier of both HBsAg und HBeAg (OR = 91.0, 95% Ci = 49.2-164.8). However, the risk of transmission was very low if the mother was an HBsAg carrier and anti-HBe positive. It was estimated that mother to infant transmission accounts for about one third of HBsAg positivity at one year of age. The implications of these findings in the planning of vaccination campaigns to prevent HBV infections are discussed.

Seroepidemiology of hepatitis B virus in the Philippines.

Hepatitis B virus markers were studied in 2,842 Philippine rural subjects from four villages in 1979-1982. The prevalence of hepatitis B surface antigen (HBsAg) and all markers for hepatitis B virus averaged 12% and 58%, respectively, in these rural populations. It is estimated that five million Filipinos are HBsAg positive. The rural age-specific HBsAg prevalence shows an "early peak" (in persons 3-4-years-old) in two communities and a "late peak" (in persons 30-40-years-old) in the other two communities. Family studies suggest that the prevalence of HBsAg and hepatitis B e antigen (HBeAg) among parents of the young children in an "early peak" and a "late peak" village cannot fully account for the difference in the patterns of prevalence of all markers, or the HBsAg marker. Horizontal intrafamilial and extrafamilial transmission may also be significant. Further research is needed on risk factors for hepatitis B virus infection.