Treating malaria in pregnancy in developing countries: priorities in clinical research and drug development.

Reducing the burden of falciparum malaria in pregnancy is an urgent international public health priority but one that involves considerable challenges. The rapidly declining effectiveness of agents known to be safe in pregnancy, and the limited efficacy, safety and pharmacokinetic data available for many other antimalarial drugs, mean that current options for the treatment of both severe and uncomplicated falciparum malaria in pregnancy are limited. This report summarizes the literature on this subject and recommends drug combinations for evaluation in Phase II/III treatment trials in pregnancy.

The safety of amodiaquine use in pregnant women.

Few antimalarial drugs have been evaluated extensively in pregnancy because of fears over toxicity. However, increasing Plasmodium falciparum resistance to chloroquine and sulfadoxine-pyrimethamine makes finding alternative antimalarials that are safe and effective in pregnancy a priority. There is a renewed interest in amodiaquine as a potential candidate, particularly as a partner drug in artemisinin-based combination therapy.

Comparison of the therapeutic efficacy of chloroquine and sulphadoxine-pyremethamine in children and pregnant women.

Objective: To compare the parasitological failure rates of under-fives and pregnant women with parasitaemia treated with chloroquine (CQ) or sulphadoxine-pyrimethamine (SP).

Methods: During a clinical trial of CQ, SP, amodiaquine (AQ) and SP plus AQ combination for malaria treatment in pregnant women in Ghana, a parallel study of treatment of children below 5 years of age with symptomatic malaria with CQ and SP was undertaken. Four hundred and fifty pregnant women with malaria parasitaemia and 203 children with malaria parasitaemia were randomized to receive CQ or SP.

Setting priorities in global child health research investments: assessment of principles and practice.

This article reviews theoretical and practical approaches for setting priorities in global child health research investments. It also provides an overview of previous attempts to develop appropriate tools and methodologies to define priorities in health research investments. A brief review of the most important theoretical concepts that should govern priority setting processes is undertaken, showing how different perspectives, such as medical, economical, legal, ethical, social, political, rational, philosophical, stakeholder driven, and others will necessarily conflict each other in determining priorities.

Comparison of active and passive case detection systems in Jepara District, Indonesia.

This study compares the role and performance of active case detection (ACD) and passive case detection (PCD) in Jepara district, Indonesia. The number of blood slides examined and positive for malaria reported from 1994-1998 was retrieved from the district surveillance registers. Age of cases, parasite species, types of drugs and dosage, and time lapse were recorded from malaria registers at the three most endemic health centres.

Is the Expanded Programme on Immunisation the most appropriate delivery system for intermittent preventive treatment of malaria in West Africa?

Objective: To investigate the coverage and equity of the Expanded Programme on Immunisation (EPI) and its effect on age schedule, seasonality of malaria risk, and linked intermittent preventive treatment (IPT) in West Africa.

Method: Secondary analyses of data from a trial of IPT in Ghana. The potential effectiveness and impact of EPI-linked IPT in West Africa was calculated using the coverage of Diptheria Pertussis Tetanus vaccination obtained from national surveys and the reported protective efficacies of IPT.

Safety of a trivalent meningococcal ACW135 vaccine among young children in Ethiopia.

A phase II open and parallel reactogenicity, immunogenicity and safety trivalent meningitis vaccine (Mencevax) trial was conducted on 413 volunteer 2-29-year-old rural residents in Ethiopia in November/December 2005. Adverse events (AE) were monitored at 1h, 1, 2, 3, 7 and 28 days after vaccination. No serious AE occurred except for burn injury (one) and severe malaria (one) after day 28.

An exploratory study of factors that affect the performance and usage of rapid diagnostic tests for malaria in the Limpopo Province, South Africa.

Background: Malaria rapid diagnostic tests (RDTs) are relatively simple to perform and provide results quickly for making treatment decisions. However, the accuracy and application of RDT results depends on several factors such as quality of the RDT, storage, transport and end user performance. A cross sectional survey to explore factors that affect the performance and use of RDTs was conducted in the primary care facilities in South Africa.

A new approach to the definition of seroconversion following vaccination in a population with high background antibody concentrations.

Licensure of meningitis vaccines is increasingly being made on the basis of safety and immunogenicity. For meningococcal vaccines, a measure of immunogenicity is seroconversion, usually defined as a four-fold increase in rSBA titre. However, this definition is likely to underestimate seroconversion in settings with high background immunity.

Haemoglobin and haematocrit: is the threefold conversion valid for assessing anaemia in malaria-endemic settings?

Background: Anaemic status is determined by haemoglobin using the HemoCue system or haematocrit measurements, and a threefold conversion is commonly used to equate the two measures (haemoglobin = haematocrit/3). The validity of this conversion in malaria endemic settings was assessed.

Methods: Concurrent measures of haemoglobin and centrifuged haematocrit in children aged 6-59 months were compared by modelling the difference between the two measures against their average.

Bacterial growth efficiency in a tropical estuary: seasonal variability subsidized by allochthonous carbon.

Bacterial growth efficiency (BGE) is a key factor in understanding bacterial influence on carbon flow in aquatic ecosystems. We report intra-annual variability in BGE, and bacteria-mediated carbon flow in the tropical Mandovi and Zuari estuaries (southwest India) and the adjoining coastal waters (Arabian Sea). BGE ranged from 3% to 61% and showed clear temporal variability with significantly (ANOVA, p < 0.

Intermittent preventive treatment for malaria in pregnancy in Africa: what's new, what's needed?

Falciparum malaria is an important cause of maternal, perinatal and neonatal morbidity in high transmission settings in Sub-Saharan Africa. Intermittent preventive treatment with sulphadoxine-pyrimethamine (SP-IPT) has proven efficacious in reducing the burden of pregnancy-associated malaria but increasing levels of parasite resistance mean that the benefits of national SP-IPT programmes may soon be seriously undermined in much of the region. Hence, there is an urgent need to develop alternative drug regimens for IPT in pregnancy.

The safety of artemisinins during pregnancy: a pressing question.

Background: An increasing number of countries in sub-Saharan Africa are changing to artemisinins combination therapy (ACT) as first or second line treatment for malaria. There is an urgent need to assess the safety of these drugs in pregnant women who may be inadvertently exposed to or actively treated with ACTs.

Objectives: To examine existing published evidence on the relationship between artemisinin compounds and adverse pregnancy outcomes and consider the published evidence with regard to the safety of these compounds when administered during pregnancy.

Estimating cause-specific mortality from community- and facility-based data sources in the United Republic of Tanzania: options and implications for mortality burden estimates.

Objective: To compare mortality burden estimates based on direct measurement of levels and causes in communities with indirect estimates based on combining health facility cause-specific mortality structures with community measurement of mortality levels.

Methods: Data from sentinel vital registration (SVR) with verbal autopsy (VA) were used to determine the cause-specific mortality burden at the community level in two areas of the United Republic of Tanzania. Proportional cause-specific mortality structures from health facilities were applied to counts of deaths obtained by SVR to produce modelled estimates.

"Trade-off" in Antarctic bacteria: limnetic psychrotrophs concede multiple enzyme expressions for multiple metal resistance.

The present study examines the metal and antibiotic resistant bacteria in ice and water from lakes east and west of the Indian base camp (Maitri) in Antarctica. The isolates from western and eastern lakes showed distinct geographical differences in properties like metal resistance and enzyme expression. This may be attributed to high organic loading in the lakes on the west of Maitri.

Over-diagnosis of malaria is not a lost cause.

Background: Recent studies have highlighted the over-diagnosis of malaria in clinical settings in Africa. This study assessed the impact of a training programme implemented as part of an intervention trial on diagnostic behaviour of clinicians in a rural district hospital in a low-moderate malaria transmission setting.

Methods: From the beginning of 2005, a randomized controlled trial (RCT) of intermittent preventive treatment for malaria in infants (IPTi) has been conducted at the study hospital.

Efficacy, safety, and tolerability of amodiaquine plus sulphadoxine-pyrimethamine used alone or in combination for malaria treatment in pregnancy: a randomised trial.

Background: The widespread increase in resistance of Plasmodium falciparum to chloroquine and sulphadoxine-pyrimethamine threatens the use of these drugs for malaria treatment in pregnancy. We aimed to assess the safety and efficacy of amodiaquine alone or in combination with sulphadoxine-pyrimethamine as alternative regimens.

Methods: Pregnant women with a gestational age of 16 weeks or more who attended antenatal clinics at a district hospital in Ghana were screened for malaria with OptiMAL dipsticks.

Core verbal autopsy procedures with comparative validation results from two countries.

Background: Cause-specific mortality statistics remain scarce for the majority of low-income countries, where the highest disease burdens are experienced. Neither facility-based information systems nor vital registration provide adequate or representative data. The expansion of sample vital registration with verbal autopsy procedures represents the most promising interim solution for this problem.

Entomological evaluation of malaria vectors at different altitudes in Hai district, northeastern Tanzania.

Entomological monitoring in four villages situated along an altitude transect in the Hai District of Northeastern Tanzania identified Anopheles arabiensis Patton as the principal vector of malaria and detected seasonal changes in vector behavior. Over a 13-mo sampling period, 10,557 mosquitoes were collected with CDC light traps, pyrethrum spray catches, and pit traps of which 5,969 (56.5%) wereAn.

Metal and antibiotic-resistance in psychrotrophic bacteria from Antarctic Marine waters.

In the wake of the findings that Antarctic krills concentrate heavy metals at ppm level, (Yamamoto et al. 1987), the Antarctic waters from the Indian side were examined for the incidence of metal and antibiotic-resistant bacteria during the austral summer (13th Indian Antarctic expedition) along the cruise track extending from 50 degrees S and 18 degrees E to 65 degrees S and 30 degrees E. The bacterial isolates from these waters showed varying degrees of resistance to antibiotics (Chloramphenicol, ampicillin, streptomycin, tetracycline and kanamycin) and metals (K(2)CrO(4), CdCl(2), ZnCl(2) and HgCl(2)) tested.

Validity of verbal autopsy procedures for determining cause of death in Tanzania.

Objectives: To validate verbal autopsy (VA) procedures for use in sample vital registration. Verbal autopsy is an important method for deriving cause-specific mortality estimates where disease burdens are greatest and routine cause-specific mortality data do not exist.

Methods: Verbal autopsies and medical records (MR) were collected for 3123 deaths in the perinatal/neonatal period, post-neonatal <5 age group, and for ages of 5 years and over in Tanzania.

Verbal autopsy: current practices and challenges.

Cause-of-death data derived from verbal autopsy (VA) are increasingly used for health planning, priority setting, monitoring and evaluation in countries with incomplete or no vital registration systems. In some regions of the world it is the only method available to obtain estimates on the distribution of causes of death. Currently, the VA method is routinely used at over 35 sites, mainly in Africa and Asia.