Scaling up towards international targets for AIDS, tuberculosis, and malaria: contribution of global fund-supported programs in 2011-2015

Objective

The paper projects the contribution to 2011–2015 international targets of three major pandemics by programs in 140 countries funded by the Global Fund to Fight AIDS, Tuberculosis and Malaria, the largest external financier of tuberculosis and malaria programs and a major external funder of HIV programs in low and middle income countries.

Design

Estimates, using past trends, for the period 2011–2015 of the number of persons receiving antiretroviral (ARV) treatment, tuberculosis case detection using the internationally approved DOTS strategy, and insecticide-treated nets (ITNs) to be delivered by programs in low and middle income countries supported by the Global Fund compared to international targets established by UNAIDS, Stop TB Partnership, Roll Back Malaria Partnership and the World Health Organisation.

Results

Global Fund-supported programs are projected to provide ARV treatment to 5.5–5.8 million people, providing 30%–31% of the 2015 international target. Investments in tuberculosis and malaria control will enable reaching in 2015 60%–63% of the international target for tuberculosis case detection and 30%–35% of the ITN distribution target in sub-Saharan Africa.

Conclusion

Global Fund investments will substantially contribute to the achievement by 2015 of international targets for HIV, TB and malaria. However, additional large scale international and domestic financing is needed if these targets are to be reached by 2015.     

Effect of investment in malaria control on child mortality in sub-Saharan Africa in 2002-2008

Background

Around 8.8 million children under-five die each year, mostly due to infectious diseases, including malaria that accounts for 16% of deaths in Africa, but the impact of international financing of malaria control on under-five mortality in sub-Saharan Africa has not been examined.

Methods and Findings

We combined multiple data sources and used panel data regression analysis to study the relationship among investment, service delivery/intervention coverage, and impact on child health by observing changes in 34 sub-Saharan African countries over 2002–2008. We used Lives Saved Tool to estimate the number of lives saved from coverage increase of insecticide-treated nets (ITNs)/indoor residual spraying (IRS). As an indicator of outcome, we also used under-five mortality rate. Global Fund investments comprised more than 70% of the Official Development Assistance (ODA) for malaria control in 34 countries. Each $1 million ODA for malaria enabled distribution of 50,478 ITNs [95%CI: 37,774–63,182] in the disbursement year. 1,000 additional ITNs distributed saved 0.625 lives [95%CI: 0.369–0.881]. Cumulatively Global Fund investments that increased ITN/IRS coverage in 2002–2008 prevented an estimated 240,000 deaths. Countries with higher malaria burden received less ODA disbursement per person-at-risk compared to lower-burden countries ($3.90 vs. $7.05). Increased ITN/IRS coverage in high-burden countries led to 3,575 lives saved per 1 million children, as compared with 914 lives in lower-burden countries. Impact of ITN/IRS coverage on under-five mortality was significant among major child health interventions such as immunisation showing that 10% increase in households with ITN/IRS would reduce 1.5 [95%CI: 0.3–2.8] child deaths per 1000 live births.

Conclusions

Along with other key child survival interventions, increased ITNs/IRS coverage has significantly contributed to child mortality reduction since 2002. ITN/IRS scale-up can be more efficiently prioritized to countries where malaria is a major cause of child deaths to save greater number of lives with available resources.     

Adoption of rapid diagnostic tests for the diagnosis of malaria, a preliminary analysis of the global fund program data, 2005 to 2010

Introduction

The World Health Organization Guidelines for the Treatment of Malaria, in 2006 and 2010, recommend parasitological confirmation of malaria before commencing treatment. Although microscopy has been the mainstay of malaria diagnostics, the magnitude of diagnostic scale up required to follow the Guidelines suggests that rapid diagnostic tests (RDTs) will be a large component. This study analyzes the adoption of rapid diagnostic testing in malaria programs supported by the Global Fund to fight AIDS, Tuberculosis and Malaria (Global Fund), the leading international funder of malaria control globally.

Methods and Findings

We analyzed, for the period 2005 to 2010, Global Fund programmatic data for 81 countries on the quantity of RDTs planned; actual quantities of RDTs and artemisinin-based combination treatments (ACTs) procured in 2009 and 2010; RDT-related activities including RDTs distributed, RDTs used, total diagnostic tests including RDTs and microscopy performed, health facilities equipped with RDTs; personnel trained to perform rapid diagnostic malaria test; and grant budgets allocated to malaria diagnosis. In 2010, diagnosis accounted for 5.2% of malaria grant budget. From 2005 to 2010, the procurement plans include148 million RDTs through 96 malaria grants in 81 countries. Around 115 million parasitological tests, including RDTs, had reportedly been performed from 2005 to 2010. Over this period, 123,132 health facilities were equipped with RDTs and 137,140 health personnel had been trained to perform RDT examinations. In 2009 and 2010, 41 million RDTs and 136 million ACTs were purchased. The ratio of procured RDTs to ACTs was 0.26 in 2009 and 0.34 in 2010.

Conclusions/significance

Global Fund financing has enabled 81 malaria-endemic countries to adopt WHO guidelines by investing in RDTs for malaria diagnosis, thereby helping improve case management of acute febrile illness in children. However, roll-out of parasitological diagnosis lags behind the roll-out of ACT-based treatment, and will require prioritization of investments.     

Costs of Eliminating Malaria and the Impact of the Global Fund in 34 Countries

Background

International financing for malaria increased more than 18-fold between 2000 and 2011; the largest source came from The Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund). Countries have made substantial progress, but achieving elimination requires sustained finances to interrupt transmission and prevent reintroduction. Since 2011, global financing for malaria has declined, fueling concerns that further progress will be impeded, especially for current malaria-eliminating countries that may face resurgent malaria if programs are disrupted.

Objectives

This study aims to 1) assess past total and Global Fund funding to the 34 current malaria-eliminating countries, and 2) estimate their future funding needs to achieve malaria elimination and prevent reintroduction through 2030.

Methods

Historical funding is assessed against trends in country-level malaria annual parasite incidences (APIs) and income per capita. Following Kizewski et al. (2007), program costs to eliminate malaria and prevent reintroduction through 2030 are estimated using a deterministic model. The cost parameters are tailored to a package of interventions aimed at malaria elimination and prevention of reintroduction.

Results

The majority of Global Fund-supported countries experiencing increases in total funding from 2005 to 2010 coincided with reductions in malaria APIs and also overall GNI per capita average annual growth. The total amount of projected funding needed for the current malaria-eliminating countries to achieve elimination and prevent reintroduction through 2030 is approximately US$8.5 billion, or about $1.84 per person at risk per year (PPY) (ranging from $2.51 PPY in 2014 to $1.43 PPY in 2030).

Conclusions

Although external donor funding, particularly from the Global Fund, has been key for many malaria-eliminating countries, sustained and sufficient financing is critical for furthering global malaria elimination. Projected cost estimates for elimination provide policymakers with an indication of the level of financial resources that should be mobilized to achieve malaria elimination goals.     

Analyzing media coverage of the global fund diseases compared with lower funded diseases (childhood pneumonia, diarrhea and measles)

Background

Pneumonia, diarrhea and measles are the leading causes of death in children worldwide, but have a disproportionately low share of international funding and media attention [1]–[3]. In comparison, AIDS, tuberculosis and malaria - diseases that also significantly affect children – receive considerably more funding and have relatively high media coverage. This study investigates the potential relationship between media agenda setting and funding levels in the context of the actual burden of disease.

Methods

The news databases Lexis Nexis, Factiva, and Google News Archive were searched for the diseases AIDS, TB and Malaria and for lower funded pediatric diseases: childhood pneumonia, diarrhea, and measles. A sample of news articles across geographic regions was also analyzed using a qualitative narrative frame analysis of how the media stories were told.

Results

There were significantly more articles addressing the Global Fund diseases compared to the lower funded pediatric diseases between 1981 and 2008 (1,344,150 versus 291,865 articles). There were also notable differences in the framing of media narratives: 1) There was a high proportion of articles with the primary purpose of raising awareness for AIDS, TB and malaria (46.2%) compared with only 17.9% of the pediatric disease articles. 2) Nearly two-thirds (61.5%) of the AIDS, tuberculosis and malaria articles used a human rights, legal or social justice frame, compared with 46.2% for the lower funded pediatric disease articles, which primarily used an ethical or moral frame.

Conclusion

This study demonstrates that lower funded pediatric diseases are presented differently in the media, both quantitatively and qualitatively, than higher funded, higher profile diseases.     

Social determinants of long lasting insecticidal hammock use among the Ra-glai ethnic minority in Vietnam: implications for forest malaria control

Background

Long-lasting insecticidal hammocks (LLIHs) are being evaluated as an additional malaria prevention tool in settings where standard control strategies have a limited impact. This is the case among the Ra-glai ethnic minority communities of Ninh Thuan, one of the forested and mountainous provinces of Central Vietnam where malaria morbidity persist due to the sylvatic nature of the main malaria vector An. dirus and the dependence of the population on the forest for subsistence - as is the case for many impoverished ethnic minorities in Southeast Asia.

Methods

A social science study was carried out ancillary to a community-based cluster randomized trial on the effectiveness of LLIHs to control forest malaria. The social science research strategy consisted of a mixed methods study triangulating qualitative data from focused ethnography and quantitative data collected during a malariometric cross-sectional survey on a random sample of 2,045 study participants.

Results

To meet work requirements during the labor intensive malaria transmission and rainy season, Ra-glai slash and burn farmers combine living in government supported villages along the road with a second home at their fields located in the forest. LLIH use was evaluated in both locations. During daytime, LLIH use at village level was reported by 69.3% of all respondents, and in forest fields this was 73.2%. In the evening, 54.1% used the LLIHs in the villages, while at the fields this was 20.7%. At night, LLIH use was minimal, regardless of the location (village 4.4%; forest 6.4%).

Discussion

Despite the free distribution of insecticide-treated nets (ITNs) and LLIHs, around half the local population remains largely unprotected when sleeping in their forest plot huts. In order to tackle forest malaria more effectively, control policies should explicitly target forest fields where ethnic minority farmers are more vulnerable to malaria.     

Malaria morbidity in children in the year after they had received intermittent preventive treatment of malaria in Mali: a randomized control trial

Background

Intermittent preventive treatment of malaria in children (IPTc) is a promising strategy for malaria control. A study conducted in Mali in 2008 showed that administration of three courses of IPTc with sulphadoxine-pyrimethamine (SP) and amodiaquine (AQ) at monthly intervals reduced clinical malaria, severe malaria and malaria infection by >80% in children under 5 years of age. Here we report the results of a follow-on study undertaken to establish whether children who had received IPTc would be at increased risk of malaria during the subsequent malaria transmission season.

Methods

Morbidity from malaria and the prevalence of malaria parasitaemia and anaemia were measured in children who had previously received IPTc with SP and AQ using similar surveillance methods to those employed during the previous intervention period.

Results

1396 of 1508 children (93%) who had previously received IPTc and 1406 of 1508 children (93%) who had previously received placebos were followed up during the high malaria transmission season of the year following the intervention. Incidence rates of clinical malaria during the post-intervention transmission season (July –November 2009) were 1.87 (95% CI 1.76 –1.99) and 1.73 (95% CI; 1.62–1.85) episodes per child year in the previous intervention and placebo groups respectively; incidence rate ratio (IRR) 1.09 (95% CI 0.99 –1.21) (P = 0.08). The prevalence of malaria infection was similar in the two groups, 7.4% versus 7.5%, prevalence ratio (PR) of 0.99 (95% CI 0.73–1.33) (P = 0.95). At the end of post-intervention malaria transmission season, the prevalence of anaemia, defined as a haemoglobin concentration<11g/dL, was similar in the two groups (56.2% versus 55.6%; PR = 1.01 [95% CI 0.91 – 1.12]) (P = 0.84).

Conclusion

IPTc with SP+AQ was not associated with an increase in incidence of malaria episodes, prevalence of malaria infection or anaemia in the subsequent malaria transmission season.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00738946","term_id":"NCT00738946"}}NCT00738946     

Malaria Prevalence in Endemic Districts of Bangladesh

Background

Following the 1971 ban of DDT in Bangladesh, malaria cases have increased steadily. Malaria persists as a major health problem in the thirteen south-eastern and north-eastern districts of Bangladesh. At present the national malaria control program, largely supported by the Global Fund for AIDS, Tuberculosis and Malaria (GFATM), provides interventions including advocacy at community level, Insecticide Treated Net (ITN) distribution, introduction of Rapid Diagnostic Tests (RDT) and combination therapy with Coartem. It is imperative, therefore, that baseline data on malaria prevalence and other malaria indicators are collected to assess the effectiveness of the interventions and rationalize the prevention and control efforts. The objective of this study was to obtain this baseline on the prevalence of malaria and bed net use in the thirteen malaria endemic districts of Bangladesh.

Methods and Principal Findings

In 2007, BRAC and ICDDR,B carried out a malaria prevalence survey in thirteen malaria endemic districts of Bangladesh. A multi-stage cluster sampling technique was used and 9750 blood samples were collected. Rapid Diagnostic Tests (RDT) were used for the diagnosis of malaria. The weighted average malaria prevalence in the thirteen endemic districts was 3.97%. In five south-eastern districts weighted average malaria prevalence rate was 6.00% and in the eight north-eastern districts weighted average malaria prevalence rate was (0.40%). The highest malaria prevalence was observed in Khagrachari district. The majority of the cases (90.18%) were P. falciparum infections. Malaria morbidity rates in five south-eastern districts was 2.94%. In eight north-eastern districts, morbidity was 0.07%.

Conclusion and Significance

Bangladesh has hypoendemic malaria with P. falciparum the dominant parasite species. The malaria situation in the five north-eastern districts of Bangladesh in particular warrants urgent attention. Detailed maps of the baseline malaria prevalence and summaries of the data collected are provided along with the survey results in full, in a supplemental information     

Performance of local light microscopy and the ParaScreen Pan/Pf rapid diagnostic test to detect malaria in health centers in Northwest Ethiopia

Background

Diagnostic tests are recommended for suspected malaria cases before treatment, but comparative performance of microscopy and rapid diagnostic tests (RDTs) at rural health centers has rarely been studied compared to independent expert microscopy.

Methods

Participants (N = 1997) with presumptive malaria were recruited from ten health centers with a range of transmission intensities in Amhara Regional State, Northwest Ethiopia during October to December 2007. Microscopy and ParaScreen Pan/Pf® RDT were done immediately by health center technicians. Blood slides were re-examined later at a central laboratory by independent expert microscopists.

Results

Of 1,997 febrile patients, 475 (23.8%) were positive by expert microscopists, with 57.7% P.falciparum, 24.6% P.vivax and 17.7% mixed infections. Sensitivity of health center microscopists for any malaria species was >90% in five health centers (four of which had the highest prevalence), >70% in nine centers and 44% in one site with lowest prevalence. Specificity for health center microscopy was very good (>95%) in all centers. For ParaScreen RDT, sensitivity was ≥90% in three centers, ≥70% in six and <60% in four centers. Specificity was ≥90% in all centers except one where it was 85%.

Conclusions

Health center microscopists performed well in nine of the ten health centers; while for ParaScreen RDT they performed well in only six centers. Overall the accuracy of local microscopy exceeded that of RDT for all outcomes. This study supports the introduction of RDTs only if accompanied by appropriate training, frequent supervision and quality control at all levels. Deficiencies in RDT use at some health centers must be rectified before universal replacement of good routine microscopy with RDTs. Maintenance and strengthening of good quality microscopy remains a priority at health center level.     

Complex Interactions between soil-transmitted helminths and malaria in pregnant women on the Thai-Burmese border

Background

Deworming is recommended by the WHO in girls and pregnant and lactating women to reduce anaemia in areas where hookworm and anaemia are common. There is conflicting evidence on the harm and the benefits of intestinal geohelminth infections on the incidence and severity of malaria, and consequently on the risks and benefits of deworming in malaria affected populations. We examined the association between geohelminths and malaria in pregnancy on the Thai-Burmese border.

Methodology

Routine antenatal care (ANC) included active detection of malaria (weekly blood smear) and anaemia (second weekly haematocrit) and systematic reporting of birth outcomes. In 1996 stool samples were collected in cross sectional surveys from women attending the ANCs. This was repeated in 2007 when malaria incidence had reduced considerably. The relationship between geohelminth infection and the progress and outcome of pregnancy was assessed.

Principal Findings

Stool sample examination (339 in 1996, 490 in 2007) detected a high prevalence of geohelminths 70% (578/829), including hookworm (42.8% (355)), A. lumbricoides (34.4% (285)) and T.trichuria (31.4% (250)) alone or in combination. A lower proportion of women (829) had mild (21.8% (181)) or severe (0.2% (2)) anaemia, or malaria 22.4% (186) (P.vivax monoinfection 53.3% (101/186)). A. lumbricoides infection was associated with a significantly decreased risk of malaria (any species) (AOR: 0.43, 95% CI: 0.23–0.84) and P.vivax malaria (AOR: 0.29, 95% CI: 0.11–0.79) whereas hookworm infection was associated with an increased risk of malaria (any species) (AOR: 1.66, 95% CI: 1.06–2.60) and anaemia (AOR: 2.41, 95% CI: 1.18–4.93). Hookworm was also associated with low birth weight (AOR: 1.81, 95% CI: 1.02–3.23).

Conclusion/Significance

A. lumbricoides and hookworm appear to have contrary associations with malaria in pregnancy.     

A randomized placebo-controlled trial of intermittent preventive treatment in pregnant women in the context of insecticide treated nets delivered through the antenatal clinic

Background

Current recommendations to prevent malaria in African pregnant women rely on insecticide treated nets (ITNs) and intermittent preventive treatment (IPTp). However, there is no information on the safety and efficacy of their combined use.

Methods

1030 pregnant Mozambican women of all gravidities received a long-lasting ITN during antenatal clinic (ANC) visits and, irrespective of HIV status, were enrolled in a randomised, double blind, placebo-controlled trial, to assess the safety and efficacy of 2-dose sulphadoxine-pyrimethamine (SP). The main outcome was the reduction in low birth weight.

Findings

Two-dose SP was safe and well tolerated, but was not associated with reductions in anaemia prevalence at delivery (RR, 0.92 [95% CI, 0.79–1.08]), low birth weight (RR, 0.99 [95% CI, 0.70–1.39]), or overall placental infection (p = 0.964). However, the SP group showed a 40% reduction (95% CI, 7.40–61.20]; p = 0.020) in the incidence of clinical malaria during pregnancy, and reductions in the prevalence of peripheral parasitaemia (7.10% vs 15.15%) (p<0.001), and of actively infected placentas (7.04% vs 13.60%) (p = 0.002). There was a reduction in severe anaemia at delivery of borderline statistical significance (p = 0.055). These effects were not modified by gravidity or HIV status. Reported ITN''s use was more than 90% in both groups.

Conclusions

Two-dose SP was associated with a reduction in some indicators, but these were not translated to significant improvement in other maternal or birth outcomes. The use of ITNs during pregnancy may reduce the need to administer IPTp. ITNs should be part of the ANC package in sub-Saharan Africa.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00209781","term_id":"NCT00209781"}}NCT00209781     

Morbidity from malaria in children in the year after they had received intermittent preventive treatment of malaria: a randomised trial

Background

Interventions that reduce exposure to malaria infection may lead to delayed malaria morbidity and mortality. We investigated whether intermittent preventive treatment of malaria in children (IPTc) was associated with an increase in the incidence of malaria after cessation of the intervention.

Methods

An individually randomised, trial of IPTc, comparing three courses of sulphadoxine pyrimethamine (SP) plus amodiaquine (AQ) with placebos was implemented in children aged 3–59 months during the 2008 malaria transmission season in Burkina Faso. All children in the trial were given a long lasting insecticide treated net; 1509 children received SP+AQ and 1505 received placebos. Passive surveillance for malaria was maintained until the end of the subsequent malaria transmission season in 2009, and active surveillance for malaria infection, anaemia and malnutrition was conducted.

Results

On thousand, four hundred and sixteen children (93.8%) and 1399 children (93.0%) initially enrolled in the intervention and control arms of the trial respectively were followed during the 2009 malaria transmission season. During the period July 2009 to November 2009, incidence rates of clinical malaria were 3.84 (95%CI; 3.67–4.02) and 3.45 (95%CI; 3.29–3.62) episodes per child during the follow up period in children who had previously received IPT or placebos, indicating a small increase in risk for children in the former intervention arm (IRR = 1.12; 95%CI 1.04–1.20) (P = 0.003). Children who had received SP+AQ had a lower prevalence of malaria infection (adjusted PR: 0.88 95%CI: 0.79–0.98) (P = 0.04) but they had a higher parasite density (P = 0.001) if they were infected. There was no evidence that the risks of moderately severe anaemia (Hb<8 g/dL), wasting, stunting, or of being underweight in children differed between treatment arms.

Conclusion

IPT with SP+AQ was associated with a small increase in the incidence of clinical malaria in the subsequent malaria transmission season.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00738946","term_id":"NCT00738946"}}NCT00738946     

Improved malaria case management through the implementation of a health facility-based sentinel site surveillance system in Uganda

Background

Heath facility-based sentinel site surveillance has been proposed as a means of monitoring trends in malaria morbidity but may also provide an opportunity to improve malaria case management. Here we described the impact of a sentinel site malaria surveillance system on promoting laboratory testing and rational antimalarial drug use.

Methodology/Principal Findings

Sentinel site malaria surveillance was established at six health facilities in Uganda between September 2006 and January 2007. Data were collected from all patients presenting to the outpatient departments including demographics, laboratory results, diagnoses, and treatments prescribed. Between the start of surveillance and March 2010, a total 424,701 patients were seen of which 229,375 (54%) were suspected of having malaria. Comparing the first three months with the last three months of surveillance, the proportion of patients with suspected malaria who underwent diagnostic testing increased from 39% to 97% (p<0.001). The proportion of patients with an appropriate decision to prescribe antimalarial therapy (positive test result prescribed, negative test result not prescribed) increased from 64% to 95% (p<0.001). The proportion of patients appropriately prescribed antimalarial therapy who were prescribed the recommended first-line regimen artemether-lumefantrine increased from 48% to 69% (p<0.001).

Conclusions/Significance

The establishment of a sentinel site malaria surveillance system in Uganda achieved almost universal utilization of diagnostic testing in patients with suspected malaria and appropriate decisions to prescribed antimalarial based on test results. Less success was achieved in promoting prescribing practice for the recommended first-line therapy. This system could provide a model for improving malaria case management in other health facilities in Africa.     

Accuracy of rapid tests for malaria and treatment outcomes for malaria and non-malaria cases among under-five children in rural Ghana

Background

WHO now recommends test-based management of malaria across all transmission settings. The accuracy of rapid diagnostic test (RDT) and the outcome of treatment based on the result of tests will influence acceptability of and adherence to the new guidelines.

Method

We conducted a study at the Kintampo hospital in rural Ghana to evaluate the performance of CareStart, a HRP-2 based RDT, using microscopy as reference. We applied IMCI treatment guidelines, restricted ACT to RDT-positive children and followed-up both RDT-positive (malaria) and RDT-negative (non-malaria) cases over 28 days.

Results

436 children were enrolled in the RDT evaluation and 391 (children with haemoglobin >8.0 gm/dl) were followed-up to assess treatment outcomes. Mean age was 25.4 months (s.d. 14.6). Sensitivity and specificity of the RDT were 100.0% and 73.0% respectively. Over the follow-up period, 32 (18.5%) RDT-negative children converted to positive, with 7 (4.0%) of them presenting with fever. More children in the non-malaria group made unscheduled visits than children in the malaria group (13.3% versus 7.7%) On all scheduled follow-up visits, proportion of children having a temperature higher than that recorded on day 0 was higher in the non-malaria group compared to the malaria group. Reports of unfavourable treatment outcomes by caregivers were higher among the non-malaria group than the malaria group.

Conclusions

The RDT had good sensitivity and specificity. However a minority of children who will not receive ACT based on RDT results may develop clinical malaria within a short period in high transmission settings. This could undermine caregivers'' and health workers'' confidence in the new guidelines. Improving the quality of management of non-malarial febrile illnesses should be a priority in the era of test-based management of malaria.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00832754","term_id":"NCT00832754"}}NCT00832754     

A systematic review and meta-analysis of the efficacy and safety of intermittent preventive treatment of malaria in children (IPTc)

Background

Intermittent preventive treatment of malaria in children less than five years of age (IPTc) has been investigated as a measure to control the burden of malaria in the Sahel and sub-Sahelian areas of Africa where malaria transmission is markedly seasonal.

Methods and Findings

IPTc studies were identified using a systematic literature search. Meta-analysis was used to assess the protective efficacy of IPTc against clinical episodes of falciparum malaria. The impact of IPTc on all-cause mortality, hospital admissions, severe malaria and the prevalence of parasitaemia and anaemia was investigated. Three aspects of safety were also assessed: adverse reactions to study drugs, development of drug resistance and loss of immunity to malaria. Twelve IPTc studies were identified: seven controlled and five non-controlled trials. Controlled studies demonstrated protective efficacies against clinical malaria of between 31% and 93% and meta-analysis gave an overall protective efficacy of monthly administered IPTc of 82% (95%CI 75%–87%) during the malaria transmission season. Pooling results from twelve studies demonstrated a protective effect of IPTc against all-cause mortality of 57% (95%CI 24%–76%) during the malaria transmission season. No serious adverse events attributable to the drugs used for IPTc were observed in any of the studies. Data from three studies that followed children during the malaria transmission season in the year following IPTc administration showed evidence of a slight increase in the incidence of clinical malaria compared to children who had not received IPTc.

Conclusions

IPTc is a safe method of malaria control that has the potential to avert a significant proportion of clinical malaria episodes in areas with markedly seasonal malaria transmission and also appears to have a substantial protective effect against all-cause mortality. These findings indicate that IPTc is a potentially valuable tool that can contribute to the control of malaria in areas with markedly seasonal transmission.     

Arthropod borne disease: the leading cause of fever in pregnancy on the Thai-Burmese border

Background

Fever in pregnancy is dangerous for both mother and foetus. In the 1980''s malaria was the leading cause of death in pregnant women in refugee camps on the Thai-Burmese border. Artemisinin combination therapy has significantly reduced the incidence of malaria in the population. The remaining causes of fever in pregnancy are not well documented.

Methodology

Pregnant women attending antenatal care, where weekly screening for malaria is routine, were invited to have a comprehensive clinical and laboratory screen if they had fever. Women were admitted to hospital, treated and followed up weekly until delivery. A convalescent serum was collected on day 21. Delivery outcomes were recorded.

Principal Findings

Febrile episodes (n = 438) occurred in 5.0% (409/8,117) of pregnant women attending antenatal clinics from 7-Jan-2004 to 17-May-2006. The main cause was malaria in 55.5% (227/409). A cohort of 203 (49.6% of 409) women had detailed fever investigations and follow up. Arthropod-borne (malaria, rickettsial infections, and dengue) and zoonotic disease (leptospirosis) accounted for nearly half of all febrile illnesses, 47.3% (96/203). Coinfection was observed in 3.9% (8/203) of women, mostly malaria and rickettsia. Pyelonephritis, 19.7% (40/203), was also a common cause of fever. Once malaria, pyelonephritis and acute respiratory illness are excluded by microscopy and/or clinical findings, one-third of the remaining febrile infections will be caused by rickettsia or leptospirosis. Scrub and murine typhus were associated with poor pregnancy outcomes including stillbirth and low birth weight. One woman died (no positive laboratory tests).

Conclusion/Significance

Malaria remains the leading cause of fever in pregnancy on the Thai-Burmese border. Scrub and murine typhus were also important causes of fever associated with poor pregnancy outcomes. Febrile pregnant women on the Thai-Burmese border who do not have malaria, pyelonephritis or respiratory tract infection should be treated with azithromycin, effective for typhus and leptospirosis.     

Declining responsiveness of Plasmodium falciparum infections to artemisinin-based combination treatments on the Kenyan coast

Background

The emergence of artemisinin-resistant P. falciparum malaria in South-East Asia highlights the need for continued global surveillance of the efficacy of artemisinin-based combination therapies.

Methods

On the Kenyan coast we studied the treatment responses in 474 children 6–59 months old with uncomplicated P. falciparum malaria in a randomized controlled trial of dihydroartemisinin-piperaquine vs. artemether-lumefantrine from 2005 to 2008. (ISRCTN88705995)

Results

The proportion of patients with residual parasitemia on day 1 rose from 55% in 2005–2006 to 87% in 2007–2008 (odds ratio, 5.4, 95%CI, 2.7–11.1; P<0.001) and from 81% to 95% (OR, 4.1, 95%CI, 1.7–9.9; P = 0.002) in the DHA-PPQ and AM-LM groups, respectively. In parallel, Kaplan-Meier estimated risks of apparent recrudescent infection by day 84 increased from 7% to 14% (P = 0.1) and from 6% to 15% (P = 0.05) with DHA-PPQ and AM-LM, respectively. Coinciding with decreasing transmission in the study area, clinical tolerance to parasitemia (defined as absence of fever) declined between 2005–2006 and 2007–2008 (OR body temperature >37.5°C, 2.8, 1.9–4.1; P<0.001). Neither in vitro sensitivity of parasites to DHA nor levels of antibodies against parasite extract accounted for parasite clearance rates or changes thereof.

Conclusions

The significant, albeit small, decline through time of parasitological response rates to treatment with ACTs may be due to the emergence of parasites with reduced drug sensitivity, to the coincident reduction in population-level clinical immunity, or both. Maintaining the efficacy of artemisinin-based therapy in Africa would benefit from a better understanding of the mechanisms underlying reduced parasite clearance rates.

Trial Registration

Controlled-Trials.com ISRCTN88705995     

School absenteeism as an adjunct surveillance indicator: experience during the second wave of the 2009 H1N1 pandemic in Quebec, Canada

Background

A school absenteeism surveillance system was implemented in the province of Quebec, Canada during the second wave of the 2009 H1N1pandemic. This paper compares this surveillance approach with other available indicators.

Method

All (3432) elementary and high schools from Quebec were included. Each school was required to report through a web-based system any day where the proportion of students absent for influenza-like illness (ILI) exceeded 10% of current school enrolment.

Results

Between October 18 and December 12 2009, 35.6% of all schools met the 10% absenteeism threshold. This proportion was greater in elementary compared to high schools (40% vs 19%) and in smaller compared to larger schools (44% vs 22%). The maximum absenteeism rate was reached the first day of reporting or within the next two days in 55% and 31% of schools respectively. The first reports and subsequent peak in school absenteeism provincially preceded the peak in paediatric hospitalization by two and one weeks, respectively. Trends in school surveillance otherwise mirrored other indicators.

Conclusion

During a pandemic, school outbreak surveillance based on a 10% threshold appears insufficient to trigger timely intervention within a given affected school. However, school surveillance appears well-correlated and slightly anticipatory compared to other population indicators. As such, school absenteeism warrants further evaluation as an adjunct surveillance indicator whose overall utility will depend upon specified objectives, and other existing capacity for monitoring and response.     

Unexpected high losses of Anopheles gambiae larvae due to rainfall

Background

Immature stages of the malaria mosquito Anopheles gambiae experience high mortality, but its cause is poorly understood. Here we study the impact of rainfall, one of the abiotic factors to which the immatures are frequently exposed, on their mortality.

Methodology/Principal Findings

We show that rainfall significantly affected larval mosquitoes by flushing them out of their aquatic habitat and killing them. Outdoor experiments under natural conditions in Kenya revealed that the additional nightly loss of larvae caused by rainfall was on average 17.5% for the youngest (L1) larvae and 4.8% for the oldest (L4) larvae; an additional 10.5% (increase from 0.9 to 11.4%) of the L1 larvae and 3.3% (from 0.1 to 3.4%) of the L4 larvae were flushed away and larval mortality increased by 6.9% (from 4.6 to 11.5%) and 1.5% (from 4.1 to 5.6%) for L1 and L4 larvae, respectively, compared to nights without rain. On rainy nights, 1.3% and 0.7% of L1 and L4 larvae, respectively, were lost due to ejection from the breeding site.

Conclusions/Significance

This study demonstrates that immature populations of malaria mosquitoes suffer high losses during rainfall events. As these populations are likely to experience several rain showers during their lifespan, rainfall will have a profound effect on the productivity of mosquito breeding sites and, as a result, on the transmission of malaria. These findings are discussed in the light of malaria risk and changing rainfall patterns in response to climate change.     

Case management of severe malaria--a forgotten practice: experiences from health facilities in Uganda

Introduction

Severe malaria is a life-threatening medical emergency and requires prompt and effective treatment to prevent death. There is paucity of published information on current practices of severe malaria case management in sub-Saharan Africa; we evaluated the management practices for severe malaria in Ugandan health facilities

Methods and Findings

We did a cross sectional survey, using multi-stage sampling methods, of health facilities in 11 districts in the eastern and mid-western parts of Uganda. The study instruments were adapted from the WHO hospital care assessment tools. Between June and August 2009, 105 health facilities were surveyed and 181 health workers and 868 patients/caretakers interviewed. None of the inpatient facilities had all seven components of a basic care package for the management of severe malaria consistently available during the 3 months prior to the survey. Referral practices were appropriate for <10% (18/196) of the patients. Prompt care at any health facility was reported by 29% (247/868) of patients. Severe malaria was correctly diagnosed in 27% of patients (233).Though the quinine dose and regimen was correct in the majority (611/868, 70.4%) of patients, it was administered in the correct volumes of 5% dextrose in only 18% (147/815). Most patients (80.1%) had several doses of quinine administered in one single 500 ml bottle of 5% dextrose. Medications were purchased by 385 (44%) patients and medical supplies by 478 patients (70.6%).

Conclusions

Management of severe malaria in Ugandan health facilities was sub-optimal. These findings highlight the challenges of correctly managing severe malaria in resource limited settings. Priority areas for improvement include triage and emergency care, referral practises, quality of diagnosis and treatment, availability of medicines and supplies, training and support supervision.