Symptomatic Malaria Cases Research Articles

Modeling the Impact of Proactive Community Case Management on Reducing Confirmed Malaria Cases in Sub-Saharan African Countries.

Malaria continues to be a major source of morbidity and mortality in sub-Saharan Africa. Timely, accurate, and effective case management is critical to malaria control. Proactive community case management (ProCCM) is a new strategy in which a community health worker "sweeps" a village, visiting households at defined intervals to proactively provide diagnostic testing and treatment if indicated. Pilot experiments have shown the potential of ProCCM for controlling malaria transmission; identifying the best strategy for administering ProCCM in terms of interval timings and number of sweeps could lead to further reductions in malaria infections. We developed an agent-based simulation to model malaria transmission and the impact of various ProCCM strategies. The model was validated using symptomatic prevalence data from a ProCCM pilot study in Senegal. Various ProCCM strategies were tested to evaluate the potential for reducing parasitologically confirmed symptomatic malaria cases in the Senegal setting. We found that weekly ProCCM sweeps during a 21-week transmission season could reduce cases by 36.3% per year compared with no sweeps. Alternatively, two initial fortnightly sweeps, seven weekly sweeps, and finally four fortnightly sweeps (13 sweeps total) could reduce confirmed malaria cases by 30.5% per year while reducing the number of diagnostic tests and corresponding costs by about 33%. Under a highly seasonal transmission setting, starting the sweeps early with longer duration and higher frequency would increase the impact of ProCCM, though with diminishing returns. The model is flexible and allows decision-makers to evaluate implementation strategies incorporating sweep frequency, time of year, and available budget.

Dynamics of asymptomatic Plasmodium falciparum and Plasmodium vivax infections and their infectiousness to mosquitoes in a low transmission setting of Ethiopia: a longitudinal observational study

ObjectiveA 15-month longitudinal study was conducted to determine the duration and infectivity of asymptomatic qPCR-detected Plasmodium falciparum and Plasmodium vivax infections in Ethiopia. MethodTotal parasite and gametocyte kinetics were determined by molecular methods; infectivity to Anopheles arabiensis mosquitoes by repeated membrane feeding assays. Infectivity results were contrasted with passively recruited symptomatic malaria cases. ResultsFor P. falciparum and P. vivax infections detected at enrolment, median durations of infection were 37 days (95% confidence interval [CI], 15-93) and 60 days (95% CI, 18-213), respectively. P. falciparum and P. vivax parasite densities declined over the course of infections. From 47 feeding assays on 22 asymptomatic P. falciparum infections, 6.4% (3/47) were infectious and these infected 1.8% (29/1579) of mosquitoes. No transmission was observed in feeding assays on asymptomatic P. vivax mono-infections (0/56); one mixed-species infection was highly infectious. Among the symptomatic cases, 4.3% (2/47) of P. falciparum and 73.3% (53/86) of P. vivax patients were infectious to mosquitoes. ConclusionThe majority of asymptomatic infections were of short duration and low parasite density. Only a minority of asymptomatic individuals were infectious to mosquitoes. This contrasts with earlier findings and is plausibly due to the low parasite densities in this population.

Rituximab Is Associated with an Increased Risk of Malaria Infection in a Malaria-Endemic Region

Rituximab has become a standard of care for the treatment of lymphoproliferative B-cell neoplasms, such as diffuse large B cell lymphoma (DLBCL). As an anti-CD20 monoclonal antibody, rituximab depletes the B lymphocyte compartment and is associated with downstream impairment in humoral immunity and increased risk of infections. While such infections are often bacterial, non-bacterial infections also do occur. Malaria is a vector-borne protozoal infection caused by plasmodium species and is endemic in most parts of sub-Saharan Africa (SSA) where HIV infection is also endemic and an independent risk factor for malaria. Most studies evaluating the safety and efficacy of rituximab were in non-endemic malaria areas with a low prevalence of HIV in the US and Europe. Therefore, the effect of rituximab-induced immunodeficiency on malaria-specific immunity and the risk of malaria among DLBCL in malaria-endemic regions is not well established. The incidence of DLBCL in SSA is increasing due to the growth and aging of the population as well as epidemic levels of HIV infection. The objective of this retrospective study is to evaluate the risk for malaria infection among DLBCL patients treated with standard chemotherapy in Malawi, a malaria-endemic country with high HIV prevalence. We performed a retrospective analysis of 96 patients, aged ≥18 with DLBCL from the Kamuzu Central Hospital (Lilongwe, Malawi) Lymphoma Study, a prospective observational cohort treated with CHOP or R-CHOP 2013-2019. Symptomatic malaria cases were determined by retrospective chart review and defined as individuals with documented positive malaria rapid diagnostic test (MRDT) or peripheral blood film (PBF) during treatment or up to one year of follow-up. Laboratory malaria cases were individuals with positive P. falciparum histidine-rich protein 2 (HRP2) antigenemia using quantitative ELISA at mid-treatment (2 months), completion (4 months), or post-treatment (12 months). HRP2 antigenemia is suggestive of current or very recent P. falciparum malaria infection. Unadjusted odds ratios were calculated for risk factors for malaria using logistic regression. Treatment regimens varied slightly with 59 patients (62%) receiving CHOP, and 37 (38%) receiving R-CHOP. Fourteen of the 96 DLBCL (14.6%) patients developed symptomatic malaria during the treatment period and the remainder remained free of malaria-associated symptoms. Symptomatic malaria was not significantly associated with age, gender, DLBCL stage, number of treatment cycles received, prior history of TB, performance status, HIV infection, or HIV RNA viral load > 1,000 copies. However, among the symptomatic malaria cases, five (36%) received CHOP, and nine (64%) received R-CHOP. Patients treated with R-CHOP were more likely to develop symptomatic malaria than CHOP patients (OR 3.38, 95% CI 1.05-12.26; p=0.03). Thirty-two (24 CHOP, 8 R-CHOP) patients were positive for malaria based on the HRP-2 antigen test and there was no correlation with rituximab treatment. However, HRP-2 antigen concentrations were significantly higher in R-CHOP patients compared to CHOP patients (2.3 OD vs 0.58 OD; p=0.01). To our knowledge, this is the first study to evaluate the effect of rituximab on malaria risk among DLBCL patients treated with chemotherapy in a malaria-endemic region. This study suggests that rituximab increases the risk of symptomatic malaria in adult DLBCL patients. Data investigating the effect of rituximab on malaria-specific antibody production is currently being analyzed. Further studies are needed to determine whether antimalarial chemoprophylaxis should be implemented to improve the comprehensive care of cancer patients residing in malaria-endemic areas.

Detection of a new Apicomplexa group from buffaloes in Mosul city, Iraq

This study was focused on the detection of a new apicomplexan parasite (Plasmodium spp.) and its clinical and haematological effects during infection of domesticated water buffaloes (Bubalis bubalis) in Mosul city, Iraq. Although Plasmodium parasites of ungulates are diverse and distributed worldwide, no data are available in Iraq about any ungulate malaria, so the current investigation endea­voured to bridge this gap in the existing body of knowledge. The study included 70 cases of domesticated water buffaloes at different ages and from both sexes that were brought to the Veterinary Teaching Hospital, University of Mosul, Mosul, Iraq. The animals were from different regions of Mosul in northern Iraq. Microscopic examination was carried out on blood smears to detect Plasmodium parasite. The nested PCR assay was also conducted using Plasmodium spp. cytochrome b gene (cytb) specific primers to confirm the infection. Results showed the presence of Plasmodium parasite in 24.28% (17/70) of cases. Plasmodium bubalis was detected by PCR in three cases from 11 buffaloes. Among infected buffaloes, the symptomatic cases of malaria were 64.5%, while only 35.5% were asymptomatic (occult) cases. Moreover, fever in 54% of cases, paleness of the mucous membranes in 36% of cases, and recumbences in 10% of cases were the clinical signs reported in symptomatic malaria cases. Anaemia and thrombocytopaenia made up the majority of the haematological abnormalities observed in malaria-infected buffaloes. This is the first report about Plasmodium bubalis in Iraqi buffaloes.

Cost-Effectiveness of PBO versus Conventional Long-Lasting Insecticidal Bed Nets in Preventing Symptomatic Malaria in Nigeria: Results of a Pragmatic Randomized Trial.

ABSTRACTInsecticide treated nets (ITNs) have been the major tool in halving malaria’s burden since 2000, but pyrethroid insecticide resistance threatens their ongoing effectiveness. In 2017, the WHO concluded that long-lasting ITNs (LLINs) with a synergist, piperonyl butoxide (PBO), provided additional public health benefit over conventional (pyrethroid-only) LLINs alone in areas of moderate insecticide resistance and endorsed them as a new class of vector control products. We performed an economic appraisal of PBO nets compared with conventional LLINs in 2019 US$ from prevention and health systems perspectives (including treatment cost offsets). We used data from a pragmatic randomized 2012–2014 trial in Nigeria with epidemiological outcomes in an area with confirmed pyrethroid resistance. Each village had 50 months of epidemiologic data, analyzed by village by month, using negative binomial regression. Compared with LLINs, although adding $0.90 per net delivered, PBO nets reduced symptomatic malaria cases by 33.4% (95% CI 10.2–50.6%). From a prevention perspective, the incremental cost-effectiveness ratio was $11 (95% CI $8–$37) per disability-adjusted life year averted. From the health systems perspective, PBO nets were significantly cost-saving relative to conventional LLINs. The benefit–cost analysis found that the added economic benefits of PBO nets over LLINs were $201 (95% CI $61–$304) for every $1 in incremental costs. Growing pyrethroid resistance is likely to strengthen the economic value of PBO nets over LLINs. Beyond their contribution to reducing malaria, PBO nets deliver outstanding economic returns for a small additional cost above conventional LLINs in locations with insecticide resistance.

Malaria and curable sexually transmitted infections in pregnant women: A two-years observational study in rural Burkina Faso.

BackgroundMalaria and curable sexually transmitted infections (STI) are the most common curable infections known to have a severe impact on pregnancy outcomes in sub-Saharan Africa. This study aims to assess the marginal and joint prevalence of symptomatic cases of malaria and STI in pregnant women living in rural settings of Burkina Faso and their associated factors, after more than a decade of the introduction of intermittent preventive treatment (IPT-SP).MethodsWe carried out an observational study in two health districts in rural Burkina, namely Nanoro and Yako. Routine data were collected during antenatal and delivery visits for all women who delivered in the year 2016 and 2017. Logistic regression models were used to assess factors associated with infections.ResultsWe collected data from 31639 pregnant women attending health facilities. Malaria, curable STI and their coinfections were diagnosed in 7747 (24.5%; 95%CI: 24.0–25.0%), 1269 (4.0%; 95%CI: 3.8–4.2%) and 388 (1.2%; 95%CI: 1.1–1.4%) women, respectively. In multivariate logistic regression, malaria occurrence was significantly higher in pregnant women < 20 years (Adjusted OR = 2.36; 95% CI: 2.07–2.69) than in women ≥30 years. The prevalence of curable STI was also significantly higher in students (Adjusted OR = 1.93; 95% CI: 1.26–2.95) and compensated workers (Adjusted OR = 1.52; 95% CI: 1.01–2.17) than in uncompensated workers. Women who received no IPT-SP had higher prevalence of malaria (Adjusted OR = 3.33; 95%CI: 3.00–3.70), curable STI (Adjusted OR = 1.96 95%CI: 1.60–2.39) and coinfections (Adjusted OR = 2.11; 95% CI: 1.50–2.95) compared to women who received SP.ConclusionMalaria and curable STI remain highly prevalent in rural settings of Burkina Faso, with young pregnant women and women who received no IPT-SP being the most affected. Prevention must be reinforced to improve maternal and infant health.

The contribution of non-malarial febrile illness co-infections to Plasmodium falciparum case counts in health facilities in sub-Saharan Africa

BackgroundThe disease burden of Plasmodium falciparum malaria illness is generally estimated using one of two distinct approaches: either by transforming P. falciparum infection prevalence estimates into incidence estimates using conversion formulae; or through adjustment of counts of recorded P. falciparum-positive fever cases from clinics. Whilst both ostensibly seek to evaluate P. falciparum disease burden, there is an implicit and problematic difference in the metric being estimated. The first enumerates only symptomatic malaria cases, while the second enumerates all febrile episodes coincident with a P. falciparum infection, regardless of the fever’s underlying cause.MethodsHere, a novel approach was used to triangulate community-based data sources capturing P. falciparum infection, fever, and care-seeking to estimate the fraction of P. falciparum-positive fevers amongst children under 5 years of age presenting at health facilities that are attributable to P. falciparum infection versus other non-malarial causes. A Bayesian hierarchical model was used to assign probabilities of malaria-attributable fever (MAF) and non-malarial febrile illness (NMFI) to children under five from a dataset of 41 surveys from 21 countries in sub-Saharan Africa conducted between 2006 and 2016. Using subsequent treatment-seeking outcomes, the proportion of MAF and NMFI amongst P. falciparum-positive febrile children presenting at public clinics was estimated.ResultsAcross all surveyed malaria-positive febrile children who sought care at public clinics across 41 country-years in sub-Saharan Africa, P. falciparum infection was estimated to be the underlying cause of only 37.7% (31.1–45.4, 95% CrI) of P. falciparum-positive fevers, with significant geographical and temporal heterogeneity between surveys.ConclusionsThese findings highlight the complex nature of the P. falciparum burden amongst children under 5 years of age and indicate that for many children presenting at health clinics, a positive P. falciparum diagnosis and a fever does not necessarily mean P. falciparum is the underlying cause of the child’s symptoms, and thus other causes of illness should always be investigated, in addition to prescribing an effective anti-malarial medication. In addition to providing new large-scale estimates of malaria-attributable fever prevalence, the results presented here improve comparability between different methods for calculating P. falciparum disease burden, with significant implications for national and global estimation of malaria burden.

Adding proactive and reactive case detection into the integrated community case management system to optimise diagnosis and treatment of malaria in a high transmission setting of Cameroon: an observational quality improvement study

ObjectiveIntegrated community case management (iCCM) of childhood illness is a powerful intervention to reduce mortality. Yet, only 29% and 59% of children with fever in sub-Saharan Africa had access to...

Prevalence of Plasmodium falciparum in symptomatic and asymptomatic children in Minna, North Central Nigeria

The prevalence of Plasmodium falciparum in asymptomatic children and its association with symptomatic malaria cases was assessed in a cohort of children from Minna, Nigeria. A total of 220 children aged 6 months to 17 years were recruited from the community and healthcare facilities. Thick and thin films of the blood samples were prepared and the parasite density was determined using the thick film while the parasite species was identified using thin film. Overall, the prevalence of Plasmodium falciparum was 70% (153/220) out of which 28% (43/153) was observed in apparently healthy children from the community (asymptomatic) and 72% (110/148) from children with fever (symptomatic). The highest parasite prevalence was observed in children 6 to 11 years 30% (22/72) for asymptomatic infection; while symptomatic infection recorded 44% (65/110) from 6 months to 5 years of age. Females tends to show a greater prevalence of Plasmodium falciparum infection with 77% (20/26) and 78% (49/63) for both asymptomatic and symptomatic infections respectively. Parasitemia was, however, not significantly associated with fever (p&gt;0.05). This study confirms that malaria remains a major cause of febrile illness during the early stages of childhood (&lt;5 years). This may however, guide case definition for clinical trials of preventive tools, as well as provide definitions that may improve the precision of measurement of the burden of malaria.

Major transcriptional changes observed in the Fulani, an ethnic group less susceptible to malaria.

The Fulani ethnic group has relatively better protection from Plasmodium falciparum malaria, as reflected by fewer symptomatic cases of malaria, lower infection rates, and lower parasite densities compared to sympatric ethnic groups. However, the basis for this lower susceptibility to malaria by the Fulani is unknown. The incidence of classic malaria resistance genes are lower in the Fulani than in other sympatric ethnic populations, and targeted SNP analyses of other candidate genes involved in the immune response to malaria have not been able to account for the observed difference in the Fulani susceptibility to P.falciparum. Therefore, we have performed a pilot study to examine global transcription and DNA methylation patterns in specific immune cell populations in the Fulani to elucidate the mechanisms that confer the lower susceptibility to P.falciparum malaria. When we compared uninfected and infected Fulani individuals, in contrast to uninfected and infected individuals from the sympatric ethnic group Mossi, we observed a key difference: a strong transcriptional response was only detected in the monocyte fraction of the Fulani, where over 1000 genes were significantly differentially expressed upon P.falciparum infection.

Longitudinal analysis of antibody responses in symptomatic malaria cases do not mirror parasite transmission in peri-urban area of Cote d'Ivoire between 2010 and 2013.

BackgroundIn the agenda towards malaria eradication, assessment of both malaria exposure and efficacy of anti-vectorial and therapeutic strategies is a key component of management and the follow-up of field interventions. The simultaneous use of several antigens (Ags) as serological markers has the potential for accurate evaluation of malaria exposure. Here we aimed to measure the longitudinal evolution of the background levels of immunity in an urban setting in confirmed clinical cases of malaria.MethodsA retrospective serological cross-sectional study on was carried out using 234 samples taken from 2010 to 2013 in peri-urban sentinel facility of Cote d’Ivoire. Antibody responses to recombinant proteins or BSA-peptides, 8 Plasmodium falciparum (PfAMA1, PfMSP4, PfMSP1, PfEMP1-DBL1α1-PF13, PfLSA1-41, PfLSA3-NR2, PfGLURP and PfCSP), one P. malariae (PmCSP) and one Anopheles gambiae salivary (gSG6-P1) antigens were measured using magnetic bead-based multiplex immunoassay (MBA). Total anti- P. falciparum IgG responses against schizont lysate from african 07/03 strain (adapted to culture) and 3D7 strain was measured by ELISA.ResultsHigh prevalence (7–93%) and levels of antibody responses to most of the antigens were evidenced. However, analysis showed only marginal decreasing trend of Ab responses from 2010 to 2013 that did not parallel the reduction of clinical malaria prevalence following the implementation of intervention in this area. There was a significant inverse correlation between Ab responses and parasitaemia (P<10−3, rho = 0.3). The particular recruitment of asymptomatic individuals in 2011 underlined a high background level of immunity almost equivalent to symptomatic patients, possibly obscuring observable yearly variations.ConclusionThe use of cross-sectional clinical malaria surveys and MBA can help to identify endemic sites where control measures have unequal impact providing relevant information about population immunity and possible decrease of transmission. However, when immunity is substantially boosted despite observable clinical decline, a larger cohort including asymptomatic recruitment is needed to monitor the impact of control measures on level of immunity.

Asymptomatic and Submicroscopic Carriage of Plasmodium knowlesi Malaria in Household and Community Members of Clinical Cases in Sabah, Malaysia.

Although asymptomatic carriage of human malaria species has been widely reported, the extent of asymptomatic, submicroscopic Plasmodium knowlesi parasitemia is unknown. In this study, samples were obtained from individuals residing in households or villages of symptomatic malaria cases with the aim of detecting submicroscopic P. knowlesi in this population. Four published molecular assays were used to confirm the presence of P. knowlesi. Latent class analysis revealed that the estimated proportion of asymptomatic individuals was 6.9% (95% confidence interval, 5.6%–8.4%). This study confirms the presence of a substantial number of asymptomatic monoinfections across all age groups; further work is needed to estimate prevalence in the wider community.

Sero-epidemiological evaluation of Plasmodium falciparum malaria in Senegal.

BackgroundIn Senegal, a significant decrease of malaria transmission intensity has been noted the last years. Parasitaemia has become lower and, therefore, more difficult to detect by microscopy. In the context of submicroscopic parasitaemia, it has become relevant to rely on relevant malaria surveillance tools to better document malaria epidemiology in such settings. Serological markers have been proposed as an essential tool for malaria surveillance. This study aimed to evaluate the sero-epidemiological situation of Plasmodium falciparum malaria in two sentinel sites in Senegal.MethodsCross-sectional surveys were carried out in Velingara (south Senegal) and Keur Soce (central Senegal) between September and October 2010. Children under 10 years old, living in these areas, were enrolled using two-level, random sampling methods. P. falciparum infection was diagnosed using microscopy. P. falciparum antibodies against circumsporozoite protein (CSP), apical membrane protein (AMA1) and merozoite surface protein 1_42 (MSP1_42) were measured by ELISA method. A stepwise logistic regression analysis was done to assess factors associated with P. falciparum antibodies carriage.ResultsA total of 1,865 children under 10 years old were enrolled. The overall falciparum malaria prevalence was 4.99% with high prevalence in Velingara of 10.03% compared to Keur Soce of 0.3%. Symptomatic malaria cases (fever associated with parasitaemia) represented 17.37%. Seroprevalence of anti-AMA1, anti-MSP1_42 and anti-CSP antibody was 38.12, 41.55 and 40.38%, respectively. The seroprevalence was more important in Velingara and increased with age, active malaria infection and area of residence.ConclusionThe use of serological markers can contribute to improved malaria surveillance in areas with declining malaria transmission. This study provided useful baseline information about the sero-epidemiological situation of malaria in Senegal and can contribute to the identification of malaria hot spots in order to concentrate intervention efforts.Trial registration number: PACTR201305000551876 (http://www.pactr.org).

High prevalence and genetic diversity of Plasmodium malariae and no evidence of Plasmodium knowlesi in Bangladesh

Although the prevalence of malaria remains high in parts of Bangladesh, there continues to be a substantial shortage of information regarding the less common malaria parasites such as Plasmodium malariae or Plasmodium knowlesi. Recent studies indicate that P. malariae may be extremely rare, and so far, there are no data on the presence (or absence) of P. knowlesi in southeastern Bangladesh. Genus- and species-specific nested polymerase chain reaction (PCR) analysis of the small subunit ribosomal RNA gene was performed to assess the presence and prevalence of P. malariae and P. knowlesi in 2,246 samples originating from asymptomatic and febrile participants of a cross-sectional and a febrile illnesses study in the Chittagong Hill Tracts in southeastern Bangladesh. P. malariae was detected in 60 samples (2.7%) corresponding to 8% of the 746 samples giving positive PCR results for Plasmodium sp., mainly because of the high prevalence (9.5%) among asymptomatic study participants testing positive for malaria. Symptomatic cases were more common (4.3% of all symptomatic malaria cases) during the dry season. Parasitemias were low (1,120-2,560/μl in symptomatic and 120-520/μl in asymptomatic carriers). Symptomatic patients presented mild to moderate symptoms like fever, chills, headache, dizziness, fatigue and myalgia.Although both the intermediate as well as the definite host are known to be endemic in southeastern Bangladesh, no evidence for the presence of P. knowlesi was found. We conclude that the role of P. malariae is highly underestimated in rural Bangladesh with major implications for malaria control and elimination strategies.

Mobile phones improve case detection and management of malaria in rural Bangladesh

BackgroundThe recent introduction of mobile phones into the rural Bandarban district of Bangladesh provided a resource to improve case detection and treatment of patients with malaria.MethodsDuring studies to define the epidemiology of malaria in villages in south-eastern Bangladesh, an area with hypoendemic malaria, the project recorded 986 mobile phone calls from families because of illness suspected to be malaria between June 2010 and June 2012.ResultsBased on phone calls, field workers visited the homes with ill persons, and collected blood samples for malaria on 1,046 people. 265 (25%) of the patients tested were positive for malaria. Of the 509 symptomatic malaria cases diagnosed during this study period, 265 (52%) were detected because of an initial mobile phone call.ConclusionMobile phone technology was found to be an efficient and effective method for rapidly detecting and treating patients with malaria in this remote area. This technology, when combined with local knowledge and field support, may be applicable to other hard-to-reach areas to improve malaria control.

Assessing the genetic diversity of the vir genes in Indian Plasmodium vivax population

Variant surface antigens (VSAs) present on the surface of parasitized erythrocytes facilitate many Plasmodium spp. to escape the host immune system during infection. Multigene families coding for VSAs exist in several Plasmodium spp. and are located on telomeric and subtelomeric regions of the chromosomes. P. vivax genome also contains a multigene superfamily vir (variant interspersed repeats), present in the subtelomeric region with a possible role in immune evasion like the var gene in P. falciparum. Blood samples from 148 symptomatic malaria cases were collected from five different regions of India, viz. Mangalore, Rourkela, Goa, Delhi and Jabalpur. P. vivax isolates (74 single infections) were sequenced for four vir genes (viz. vir 27, vir 4, vir 12 and vir 21) and analyzed for the genetic variability existing in different populations of India. The results indicate that vir genes in different P. vivax populations in India are highly divergent both within and between the isolates. High levels of single nucleotide polymorphisms (SNPs) were observed attributing to the existing polymorphism for all the four vir genes studied across the population. Detailed knowledge of the genetic variation among the vir genes will help in understanding the evolutionary aspects of vir genes and may also provide basis for understanding the disease chronicity.

Estimated financial and human resources requirements for the treatment of malaria in Malawi

BackgroundMalaria fever is a common medical presentation and diagnosis in Malawi. The national malaria policy supports self-diagnosis and self-medication for uncomplicated malaria with first line anti-malaria drugs. While a qualitative appreciation of the burden of malaria on the health system is recognized, there is limited quantitative estimation of the burden malaria exacts on the health system, especially with regard to human resources and financial burden on Malawi.MethodsThe burden of malaria was assessed based on estimated incidence rates for a high endemic country of which Malawi is one. Data on the available human resources and financial resources committed towards malaria from official Malawi government documents and programme reports were obtained. The amount of human and financial resources that would be required to treat 65% or 85% of symptomatic malaria cases as per the Roll Back Malaria partnership and the US President's Malaria Initiative targets.ResultsBased on a malaria incidence rate of 1.4 episodes per year per person it was estimated that there would be 3.71 million symptomatic episodes of malaria among children <5 years of age based on mid-2007 census projections. At 0.59 episodes each year per person there would be 2.13 million episodes in the 5 to 14 year age group and 1.02 million episodes in. There would be 761,848 malaria cases when HIV is not factored in among those 15 years of age or above; this figure rose to 2.2 million when the impact of HIV in increasing malaria incidence was considered. The prevalence of HIV has resulted in 42.3% increase in symptomatic malaria cases. Treating 65% to 85% of cases would result in using 8.9% to 12.2% of the national health budget or 22.2% to 33.2% of the national drug budget. Furthermore, having 65% to 85% of cases treated at a health facility would consume 55.5% to 61.1% of full-time equivalents of all the clinicians registered in the country. While this study's estimated time of 5 and 10 minutes per consultation may differ in actual practice, due to time constraints patients may not be seen for longer consultation in resources limited settings.ConclusionMalaria exacts a heavy toll on the health system in Malawi. The national recommendation of self-medication with first-line drug for uncomplicated malaria is justified as there are not enough clinicians to provide clinical care for all cases. The Malawi Ministry of Health's promotion of malaria drug prescription including other lower cadre health workers may be justified.

Aggressive active case detection: a malaria control strategy based on the Brazilian model

Since 1996, the Brazilian Ministry of Health has adopted a malaria control strategy known as aggressive active case detection (AACD) in which most or all members of every community are tested and treated for malaria on a monthly basis. The strategy attempts to identify and treat cases of asymptomatic malaria, which, if untreated, continue to transmit the infection. Malaria remains uncontrolled because almost all health care systems in the world rely on passive case detection: the treatment of only symptomatic cases of malaria. Research has shown conclusively that asymptomatic cases exist in any population where malaria transmission is stable and incidence is high: therefore passive case detection simply will not succeed in breaking the cycle of transmission. Numerous case studies show that malaria has been successfully controlled on a regional or national level by mass blood surveys. AACD is an effective malaria control strategy if used in conjunction with other methods, especially when (1) an effective treatment exists, (2) influx of potential carriers of the infection can be monitored, and (3) people are inclined to cooperate with monthly blood testing. AACD requires access to rapid diagnostic tests (RDTs), microscopy supplies, extensive human resources, and prompt, affordable, and effective treatment. AACD is compared to PCD in terms of clinical efficacy and cost effectiveness in a case study of malaria in the Brazilian Yanomami Indians. Where it is feasible, AACD could drastically reduce the incidence of malaria and should be an integral part of the World Health Organization's Roll Back Malaria strategy.

Plasmodium falciparum: Malaria Morbidity Is Associated with Specific Merozoite Surface Antigen 2 Genotypes

Plasmodium falciparum merozoite surface antigen 2 (MSA2) is considered a vaccine candidate in a subunit vaccine against blood stage malaria. In order to test if a specific genotype of the highly polymorphic MSA2 is associated with disease, we conducted a case-control study in a malaria endemic area of Papua New Guinea involving 227 individuals, mostly children under the age of 10 years, All cases and controls were genotyped by polymerase chain reaction for their respective MSA2 genotypes. We report that at the time of the study parasites carrying the FC27-like genotype were twice as likely to be found in symptomatic malaria cases than in asymptomatic controls. Mixed genotype infections were significantly less frequent in symptomatic malaria infections. One individual allele (WOS10) of the FC27 family was found only in cases. This may be a form of P. falciparum infrequently encountered and may cause morbidity due to lack of immunity to it. This study provides evidence that MSA2 is involved in the morbidity of malaria and supports the inclusion of MSA2 in a subunit vaccine.