Frank Baiden

Pre-referral rectal artesunate to prevent death and disability in severe malaria: a placebo-controlled trial

Summary Background Most malaria deaths occur in rural areas. Rapid progression from illness to death can be interrupted by prompt, effective medication. Antimalarial treatment cannot rescue terminally ill patients but could be effective if given earlier. If patients who cannot be treated orally are several hours from facilities for injections, rectal artesunate can be given before referral and acts rapidly on parasites. We investigated whether this intervention reduced mortality and permanent disability. Methods In Bangladesh, Ghana, and Tanzania, patients with suspected severe malaria who could not be treated orally were allocated randomly to a single artesunate (n=8954) or placebo (n=8872) suppository by taking the next numbered box, then referred to clinics at which injections could be given. Those with antimalarial injections or negative blood smears before randomisation were excluded, leaving 12 068 patients (6072 artesunate, 5996 placebo) for analysis. Primary endpoints were mortality, assessed 7–30 days later, and permanent disability, reassessed periodically. All investigators were masked to group assignment. Analysis was by intention to treat. This study is registered in all three countries, numbers ISRCTN83979018, 46343627, and 76987662. Results Mortality was 154 of 6072 artesunate versus 177 of 5996 placebo (2·5% vs 3·0%, p=0·1). Two versus 13 (0·03% vs 0·22%, p=0·0020) were permanently disabled; total dead or disabled: 156 versus 190 (2·6% vs 3·2%, p=0·0484). There was no reduction in early mortality (56 vs 51 deaths within 6 h; median 2 h). In patients reaching clinic within 6 h (median 3 h), pre-referral artesunate had no significant effect on death after 6 h or permanent disability (71/4450 [1·6%] vs 82/4426 [1·9%], risk ratio 0·86 [95% CI 0·63–1·18], p=0·35). In patients still not in clinic after more than 6 h, however, half were still not there after more than 15 h, and pre-referral rectal artesunate significantly reduced death or permanent disability (29/1566 [1·9%] vs 57/1519 [3·8%], risk ratio 0·49 [95% CI 0·32–0·77], p=0·0013). Interpretation If patients with severe malaria cannot be treated orally and access to injections will take several hours, a single inexpensive artesunate suppository at the time of referral substantially reduces the risk of death or permanent disability. Funding UNICEF/UNDP/World Bank Special Programme for Research and Training in Tropical Diseases (WHO/TDR); WHO Global Malaria Programme (WHO/GMP); Sall Family Foundation; the European Union (QLRT-2000-01430); the UK Medical Research Council; USAID; Irish Aid; the Karolinska Institute; and the University of Oxford Clinical Trial Service Unit (CTSU).

Setting international standards for verbal autopsy

In many countries most deaths occur at home. Such countries often have civil registration systems that are limited or non-existent and therefore most deaths go unrecorded. Countries that cannot record the number of people who die or why they die cannot realize the full potential of their health systems. Health systems need reliable numbers and causes of death to function properly. But in these circumstances – in the absence of a complete picture of the population’s health – there are tools and techniques that can be used to obtain a fairly accurate representation of mortality trends. It takes a long time for countries to achieve a fully functioning civil registration system with medical certification of cause of death. In the meantime, more and more countries are using verbal autopsies (VA) to meet the information needs of their health systems.1 Verbal autopsy is a method of ascertaining probable causes of a death based on an interview with primary caregivers about the signs, symptoms and circumstances preceding that death. Different institutions have been researching and developing all aspects of the verbal autopsy process over the past two decades. We have also been working on this process, particularly to improve the questionnaire and the methods of analysing the resulting information. However, this has been a largely uncoordinated effort and one that has not reached consensus on what to cover in the interview and how to analyse the results, despite previous attempts to promote standard tools.2–4 The main consequence of this failure to agree on a standard approach is that now we cannot compare results from different countries. Currently, 36 Demographic Surveillance Sites (DSS) in 20 countries, the Sample Registration System (SRS) sites in India, and the Disease Surveillance Points (DSP) in China regularly use VA on a large scale, primarily to assess the causes-of-death structure of a defined population.1 Despite such a widespread use of verbal autopsy, we are unable to assess how consistent and reliable the data are. We are also unable to replicate procedures used to assign cause of death. Because verbal autopsy data sets are not widely shared, it is impossible to independently assess the quality of the assignment. Really useful validation studies are rare and verbal autopsy research is often done on small and non-representative samples of the population. The Millennium Development Goals (MDG) have put pressure on countries to track their progress in terms of population health. But to track that progress, countries need reliable numbers. In other words, they need a strong empirical basis for cause-specific mortality data. This is essential for evaluating the impact of disease control programmes and major global health initiatives. One way of dealing with incomplete information is to use models of mortality patterns. But cause-of-death information predicted by such models is not suitable for monitoring progress on what works and what does not.5 That leaves verbal autopsy as the only practical option in these countries and one that will play a key role in tracking progress towards the MDGs. Agreement on a core set of verbal autopsy tools (including technical standards and guidelines for their use) and their widespread adoption is needed now. To tackle this challenge, WHO led an expert group of researchers, data users, and other stakeholders, with sponsorship from the Health Metrics Network (HMN), in developing the necessary standards. The expert group systematically reviewed, debated, and condensed the accumulated experience and evidence from the most widely-used and validated procedures. This synthesis was done to achieve a high degree of consistency and comparability across verbal autopsy data sets. WHO has now published the results of this collaboration as: Verbal autopsy standards: ascertaining and attributing cause of death. The new standards include: Verbal autopsy questionnaires for three age groups (under four weeks; four weeks to 14 years; and 15 years and above); Cause-of-death certification and coding resources consistent with the International Classification of Diseases and Related health Problems, tenth revision (ICD-10); and A cause-of-death list for verbal autopsy prepared according to the ICD-10. The content is freely available on the WHO web site (www.who.int) and will be distributed in print; and incorporated into HMN’s resource kit. This is an important publication, but it is not the last word on verbal autopsy methods. Research is needed to validate these standard core procedures in several countries with different patterns of mortality. Other areas of research include further development of items included in questionnaires, and automated methods for assigning causes of death from verbal autopsy that remove human bias, while producing replicable and valid results.6 Operational issues need addressing: sampling methods and size when using verbal autopsy tools in research demographic surveillance sites; sample or sentinel registration; censuses; and household surveys. Research is also required when adapting these questionnaires to specific situations in different countries, taking into account relevant cultural, epidemiological and administrative considerations. WHO is working with partners to do this research and develop guidelines on these issues. With time, this guidance and experience will better inform the users of verbal autopsy, and improve the comparability and consistency of its results. For the present, we urge that these new international consensus standards become the foundation of verbal autopsy practices wherever possible. ■

Voluntary counseling and HIV testing for pregnant women in the Kassena-Nankana district of northern Ghana: Is couple counseling the way forward?

Abstract This study reports the results of a cross-sectional questionnaire survey undertaken in the Kassena-Nankana district of Ghana to assess the perception and attitude of 270 antenatal clinic attendants towards voluntary counseling and HIV testing. It was found that although 92.6% (95% CI 88.8–95.4) of respondents indicated a willingness to get tested, only 51% (95% CI 45.0–57.2) considered HIV testing for pregnant women to be useful. Most (93.6%) indicated they would like their husbands (partners) to know the result of the test and 52.2% indicated that their husbands would be willing to accompany them to antenatal clinic (ANC) at least once during the pregnancy. The perception of the usefulness of HIV testing (OR = 8.5, 95% CI 1.8–40.0), the willingness to disclose test result to the husband (OR = 13.3, 95% CI 4.0–44.5) and perceived willingness of husband to accompany wife to antenatal clinic (OR = 5.2, 95% CI 1.4–19.8) were found to be independent predictors of a womans willingness to get tested. The willingness to disclose test result to husband (OR 3.2, 95% CI 1.1–10.5) and knowledge of at least one mode of MTCT HIV transmission (OR = 2.1, 95% CI 1.2–3.6) were found to be independent predictors of a womans perception that getting tested was useful. The results suggest that for pregnant women in this district, the willingness to get tested for HIV does not equate with the perception of the tests usefulness, and that spouses are likely to exert strong influence on the attitude of pregnant women towards VCT. Couple counseling facilitated through couple-friendly ANC services should be explored as strategy for the intended VCT program in this district.

Trend and causes of neonatal mortality in the Kassena–Nankana district of northern Ghana, 1995–2002

Objectives  To describe the trend and causes of neonatal deaths in a rural district in northern Ghana.

Demographic Surveillance Sites and emerging challenges in international health

At present the long-term social economic and demographic impact of major diseases in developing countries can only be estimated using models since there are no empirical data on age and cause-specific morbidity and mortality. Reliable estimates require the input of accurate data into the models from as many geographical zones as possible. With the collapse of vital registration systems and the rudimentary state of health information systems in most of the developing world estimated projections are sometimes based on educated guesses and intuition rather than fact. The investment needed to improve health information in these countries is unlikely to be made in the near future. Strong national health research systems are needed to improve health. For developing countries to indigenize health research systems it is essential to build capacity.3 A local cadre of research scientists is urgently needed particularly in epidemiology statistics immunology and the clinical sciences. Global disease control initiatives exist in countries where there are fewer than four epidemiologists and only one statistician. Training abroad has been an invaluable stopgap measure but demand has consistently outstripped supply. The question remains: where is the next generation of research scientists in the developing world going to be trained? (excerpt)

Using lay counsellors to promote community-based voluntary counselling and HIV testing in rural northern Ghana: a baseline survey on community acceptance and stigma.

Access to voluntary counselling and HIV testing (VCT) remains limited in most parts of Ghana with rural populations being the least served. Services remain facility-based and employ the use of an ever-dwindling number of health workers as counsellors. This study assessed approval for the use of lay counsellors to promote community-based voluntary counselling and testing for HIV and the extent of HIV/AIDS-related stigma in the Kassena-Nankana district of rural northern Ghana. A cross-sectional questionnaire survey was conducted. Logistic regression was used to identify predictors of the tendency to stigmatize people living with HIV/AIDS (PLWHAs). Focus group discussions were held and analytical coding of the data performed. The majority (91.1%) of the 403 respondents indicated a desire to know their HIV status. Most (88.1%) respondents considered locations outside of the health facility as preferred places for VCT. The majority (98.7%) of respondents approved the use of lay counsellors. About a quarter (24%) of respondents believed that it was possible to acquire HIV through sharing a drinking cup with a PLWHA. About half (52.1%) of the respondents considered that a teacher with HIV/AIDS should not be allowed to teach, while 77.2% would not buy vegetables from a PLWHA. Respondents who believed that sharing a drinking cup with a PLWHA could transmit HIV infection (OR 2.50, 95%CI 1.52-4.11) and respondents without formal education (OR 2.94, 95%CI 1.38-6.27) were more likely to stigmatize PLWHAs. In contrast, respondents with knowledge of the availability of antiretroviral (ARV) drugs were less likely to do so (OR 0.40, 95%CI 0.22-0.73). Findings from the thirteen focus group discussions reinforced approval for community-based VCT and lay counsellors but revealed concerns about stigma and confidentiality. In conclusion, community-based VCT and the use of lay counsellors may be acceptable options for promoting access. Interventional studies are required to assess feasibility and cost-effectiveness.

Factors influencing the intention of women in rural Ghana to adopt postpartum family planning

BackgroundUptake of postpartum family planning (PPFP) remains low in sub-Saharan Africa and very little is known about how pregnant women arrive at their decisions to adopt PPFP. This information is needed to guide the development of interventions to promote PPFP.MethodsWe conducted a survey among pregnant women attending antenatal clinics in a rural district in Ghana. We used univariate and multivariate logistic regression analysis to explore how knowledge of various family planning (FP) methods, past experience with their use and the acceptability of PPFP to male partners and close relations influenced the intention of pregnant women to adopt PPFP.ResultsWe interviewed 1914 pregnant women in four health facilities. About 84% considered PPFP acceptable, and 70% intended to adopt a method. The most preferred methods were injectables (31.5%), exclusive breastfeeding (16.7%), and oral contraceptive pills (14.8%). Women whose first choice of PPFP method were injectables were more likely to be women who had had past experience with its use (O.R = 2.07, 95% C.I. 1.50-2.87). Acceptability of PPFP by the pregnant woman (O.R. = 3.21, 1.64-6.26), perception of partner acceptability (O.R. = 3.20, 1.94-5.48), having had prior experience with the use of injectables (O.R. = 3.72, 2.61-5.30) were the strongest predictors of the intention to adopt PPFP. Conversely women who knew about the diaphragm (O.R. = 0.59, 0.38-0.93) and those who had past experience with IUD use (O.R. = 0.13, 0.05-0.38) were less likely to want to adopt PPFP.ConclusionsAcceptability of PPFP to the pregnant woman, male partner approval, and past experience with the use of injectables are important factors in the PPFP decisions of women in this population. Antenatal and early postnatal care need to be adapted to take these factors into consideration.

An Evaluation of the Clinical Assessments of Under-Five Febrile Children Presenting to Primary Health Facilities in Rural Ghana

Background The shift to test-based management of malaria represents an important departure from established practice under the Integrated Management of Childhood Illnesses (IMCI). The possibility of false results of tests for malaria and co-morbidity, however, make it important that guidelines in IMCI case assessment are still followed. Methods and Findings We conducted a cross-sectional observational study to evaluate current practices in IMCI-based assessment of febrile children in 10 health centres and 5 district hospitals, with follow up of a subset of children to determine day 7–10 post-treatment clinical outcome. Clinical consultation, examination and prescribing practices were recorded using a checklist by trained non-medical observers. The facility case management of 1,983 under-five years old febrile children was observed and 593 followed up at home on days 5–10. The mean number of tasks performed from the 11 tasks expected to be done by the IMCI guidelines was 6 (SD 1.6). More than 6 tasks were performed in only 35% of children and this varied substantially between health facilities (range 3–85%). All 11 tasks were performed in only 1% of children. The most commonly performed tasks were temperature measurement (91%) and weighing (88%). Respiratory rate was checked in only 4% of children presenting with cough or difficulty in breathing. The likelihood of performing “better than average number of tasks” (>6) was higher when the consultation was done by medical assistants than doctors (O.R. = 3.16, 1.02–9.20). The number of tasks performed during assessment did not, however, influence clinical outcome (O.R. = 1.02, 0.83–1.24). Conclusion Facility-tailored interventions are needed to improve adherence to IMCI guidelines incorporating test-based management of malaria. Studies are needed to re-evaluate the continued validity of tasks defined in IMCI case assessment guidelines.

Acceptability of Rapid Diagnostic Test-Based Management of Malaria among Caregivers of Under-Five Children in Rural Ghana

Introduction WHO now recommends test-based management of malaria (TBMM) across all age-groups. This implies artemisinin-based combination treatment (ACT) should be restricted to rapid diagnostic test (RDT)-positive cases. This is a departure from what caregivers in rural communities have been used to for many years. Methods We conducted a survey among caregivers living close to 32 health centres in six districts in rural Ghana and used logistic regression to explore factors likely to influence caregiver acceptability of RDT based case management and concern about the denial of ACT on account of negative RDT results. Focus group discussions were conducted to explain the quantitative findings and to elicit further factors. Results A total of 3047 caregivers were interviewed. Nearly all (98%) reported a preference for TBMM over presumptive treatment. Caregivers who preferred TBMM were less likely to be concerned about the denial of ACT to their test-negative children (O.R. 0.57, 95%C.I. 0.33–0.98). Compared with caregivers who had never secured national health insurance cover, caregivers who had valid (adjusted O.R. 1.30, 95% CI 1.07–1.61) or expired (adjusted O.R. 1.38, 95% CI 1.12–1.73) insurance cover were more likely to be concerned about the denial of ACT to their RDT-negative children. Major factors that promote TBMM acceptability include the perception that a blood test at health centre level represents improvement in the quality of care, leads to improvement in treatment outcomes, and offers opportunity for better communication between health workers and caregivers. Acceptability is also enhanced by engaging caregivers in the procedures of the test. Apprehensions about negative health worker attitude could however undermine acceptance. Conclusion Test (RDT)-based management of malaria in under-five children is likely to be acceptable to caregivers in rural Ghana. The quality of caregiver-health worker interaction needs to be improved if acceptability is to be sustained.

Would rational use of antibiotics be compromised in the era of test-based management of malaria?

Editorial: L’utilisation rationnelle des antibiotiques sera‐t‐elle compromise dans l’ère de la prise en charge de la malaria basée sur les tests?