HIV-1 infection and antibodies to Plasmodium falciparum in adults.

BACKGROUND: Coinfection with human immunodeficiency virus (HIV) may increase susceptibility to malaria by compromising naturally acquired immunity. METHODS: In 339 adults (64% HIV infected), we measured antibodies to Plasmodium falciparum variant surface antigens (VSA) and antibodies that opsonise infected erythrocytes using parasite lines FCR3, E8B, and R29, and antibodies to merozoite antigens AMA-1 and MSP2. We determined the relationship between malaria antibodies, HIV infection, markers of immune compromise, and risk of incident parasitemia. RESULTS: HIV-infected adults had significantly lower mean levels of opsonizing antibody to all parasite lines (P < .0001), and lower levels of antibody to AMA-1 (P = .01) and MSP2 (P < .0001). Levels of immunoglobulin G (IgG) to VSA were not affected by HIV status. Opsonising antibody titres against some isolates were positively correlated with CD4 count. There were negative associations between human immunodeficiency virus type 1 (HIV-1) viral load and opsonizing antibodies to FCR3 (P = .04), and levels of IgG to AMA-1 (P ≤ .03) and MSP2-3D7 (P = .05). Lower opsonizing antibody levels on enrollment were seen in those who became parasitemic during follow-up, independent of HIV infection (P ≤ .04 for each line). CONCLUSIONS: HIV-1 infection decreases opsonizing antibodies to VSA, and antibody to merozoite antigens. Opsonizing antibodies were associated with lack of parasitemia during follow up, suggesting a role in protection.

Operational research to inform a sub-national surveillance intervention for malaria elimination in Solomon Islands.

BACKGROUND: Successful reduction of malaria transmission to very low levels has made Isabel Province, Solomon Islands, a target for early elimination by 2014. High malaria transmission in neighbouring provinces and the potential for local asymptomatic infections to cause malaria resurgence highlights the need for sub-national tailoring of surveillance interventions. This study contributes to a situational analysis of malaria in Isabel Province to inform an appropriate surveillance intervention. METHODS: A mixed method study was carried out in Isabel Province in late 2009 and early 2010. The quantitative component was a population-based prevalence survey of 8,554 people from 129 villages, which were selected using a spatially stratified sampling approach to achieve uniform geographical coverage of populated areas. Diagnosis was initially based on Giemsa-stained blood slides followed by molecular analysis using polymerase chain reaction (PCR). Local perceptions and practices related to management of fever and treatment-seeking that would impact a surveillance intervention were also explored using qualitative research methods. RESULTS: Approximately 33% (8,554/26,221) of the population of Isabel Province participated in the survey. Only one subject was found to be infected with Plasmodium falciparum (Pf) (96 parasites/µL) using Giemsa-stained blood films, giving a prevalence of 0.01%. PCR analysis detected a further 13 cases, giving an estimated malaria prevalence of 0.51%. There was a wide geographical distribution of infected subjects. None reported having travelled outside Isabel Province in the previous three months suggesting low-level indigenous malaria transmission. The qualitative findings provide warning signs that the current community vigilance approach to surveillance will not be sufficient to achieve elimination. In addition, fever severity is being used by individuals as an indicator for malaria and a trigger for timely treatment-seeking and case reporting. In light of the finding of a low prevalence of parasitaemia, the current surveillance system may not be able to detect and prevent malaria resurgence. CONCLUSION: An adaption to the malERA surveillance framework is proposed and recommendations made for a tailored provincial-level surveillance intervention, which will be essential to achieve elimination, and to maintain this status while the rest of the country catches up.

Exploring provider and community responses to the new malaria diagnostic and treatment regime in Solomon Islands.

BACKGROUND: Improvements in availability and accessibility of artemisinin-based combination therapy (ACT) for malaria treatment and the emergence of multi-drug-resistant parasites have prompted many countries to adopt ACT as the first-line drug. In 2009, Solomon Islands (SI) likewise implemented new national treatment guidelines for malaria. The ACT, Coartem® (artemether-lumefantrine) is now the primary pharmacotherapy in SI for Plasmodium falciparum malaria, Plasmodium vivax malaria or mixed infections. Targeted treatment is also recommended in the new treatment regime through maintenance of quality microscopy services and the introduction of Rapid Diagnostic Tests (RDTs). Ascertaining the factors that influence community and provider acceptance of and adherence to the new treatment regime will be vital to improving the effectiveness of this intervention and reducing the risk of development of drug resistance. METHODS: In order to understand community and prescriber perceptions and acceptability of the new diagnostic and treatment interventions, 12 focus group discussions (FGDs) and 12 key informant interviews (KII) were carried out in rural and urban villages of Malaita Province, Solomon Islands four months subsequent to roll out of these interventions. RESULTS: Lack of access to microscopy or distrust in the accuracy of diagnostic tools were reported by some participants as reasons for the ongoing practice of presumptive treatment of malaria. Lack of confidence in RDT accuracy has negatively impacted its acceptability. Coartem® had good acceptability among most participants, however, some rural participants questioned its effectiveness due to lack of side effects and the larger quantity of tablets required to be taken. Storing of left over medication for subsequent fever episodes was reported as common. CONCLUSION: To address these issues, further training and supportive supervision of healthcare workers will be essential, as will the engagement of influential community members in health promotion activities to improve acceptability of RDTs and adherence to the new treatment regime. Exploring the extent of these issues beyond the study population must be a priority for malaria programme managers. Practices such as presumptive treatment and the taking of sub-curative doses are of considerable concern for both the health of individuals and the increased risk it poses to the development of parasite resistance to this important first-line treatment against malaria.

Malaria elimination in Isabel Province, Solomon Islands: establishing a surveillance-response system to prevent introduction and reintroduction of malaria.

BACKGROUND: The Solomon Islands National Malaria Programme is currently focused on intensified control and progressive elimination. Recent control efforts in Isabel Province have reduced their malaria incidence to 2.6/1,000 population in 2009 1 whereas most neighbouring provinces have much higher incidences. A malaria surveillance-response system that involves testing all travellers entering Isabel Province using rapid diagnostic tests (RDT) to prevent cases being imported had been proposed by local health authorities. This study provides information on the feasibility and acceptability of implementing a new approach of surveillance and response in the context of low levels of indigenous malaria transmission in Isabel Province. METHODS: A total of 13 focus group discussions (FGD) and 22 key informant interviews (KII) were conducted in Isabel Province, Solomon Islands. Key topics included: the travel patterns of people to, from and within Isabel Province; the acceptability, community perceptions, attitudes and suggestions towards the proposed surveillance programme; and management of suspected malaria cases. This information was triangulated with data obtained from port authorities, airlines and passenger ships travelling to and from Isabel Province in the preceding two years. RESULTS: Travel within Isabel Province and to and from other provinces is common with marked seasonality. The majority of inter-provincial travel is done on scheduled public transport; namely passenger ships and aircrafts. In Isabel Province there is a healthy community spirit as well as high concern regarding malaria and its importation and there is currently effective malaria passive case detection and management. Conducting malaria screening at ports and airports would be acceptable to the community. CONCLUSION: A robust surveillance-response system is essential when moving towards malaria elimination. Many factors contribute positively towards the feasibility of an RDT based malaria surveillance system in Isabel Province. Due to financial and logistical restraints local health authorities have concluded that a system of community-based vigilance to identify new arrivals in villages and direct them to have malaria testing is more feasible than formal screening at ports and airports. A surveillance response system to prevent introduction of malaria into Isabel Province can be integrated into the National Malaria Control Programme provided the operational steps are carefully planned with regards to human and financial resources.

Population screening for glucose-6-phosphate dehydrogenase deficiencies in Isabel Province, Solomon Islands, using a modified enzyme assay on filter paper dried bloodspots.

BACKGROUND: Glucose-6-phosphate dehydrogenase deficiency poses a significant impediment to primaquine use for the elimination of liver stage infection with Plasmodium vivax and for gametocyte clearance, because of the risk of life-threatening haemolytic anaemia that can occur in G6PD deficient patients. Although a range of methods for screening G6PD deficiency have been described, almost all require skilled personnel, expensive laboratory equipment, freshly collected blood, and are time consuming; factors that render them unsuitable for mass-screening purposes. METHODS: A published WST8/1-methoxy PMS method was adapted to assay G6PD activity in a 96-well format using dried blood spots, and used it to undertake population screening within a malaria survey undertaken in Isabel Province, Solomon Islands. The assay results were compared to a biochemical test and a recently marketed rapid diagnostic test. RESULTS: Comparative testing with biochemical and rapid diagnostic test indicated that results obtained by filter paper assay were accurate providing that blood spots were assayed within 5 days when stored at ambient temperature and 10 days when stored at 4 degrees. Screening of 8541 people from 41 villages in Isabel Province, Solomon Islands revealed the prevalence of G6PD deficiency as defined by enzyme activity < 30% of normal control was 20.3% and a prevalence of severe deficiency that would predispose to primaquine-induced hemolysis (WHO Class I-II) of 6.9%. CONCLUSIONS: The assay enabled simple and quick semi-quantitative population screening in a malaria-endemic region. The study indicated a high prevalence of G6PD deficiency in Isabel Province and highlights the critical need to consider G6PD deficiency in the context of P. vivax malaria elimination strategies in Solomon Islands, particularly in light of the potential role of primaquine mass drug administration.

An indigenous case of Plasmodium ovale infection in Sri Lanka.

Plasmodium ovale, which is generally prevalent only in the African region, has been emerging in the Asian and southeast Asian regions. It has not been reported in Sri Lanka. We report, to our knowledge, an indigenous case of P. ovale infection in Sri Lanka. This patient, who was diagnosed by a polymerase chain reaction, had no history of travel overseas or receipt of a transfusion of blood or any blood products, which makes this a likely case of indigenous transmission. This incidental finding of a P. ovale infection has implications for malaria control in the country and highlights the need to rigorously monitor malaria incidence, as well as prevalent Plasmodium species, with newer and more reliable diagnostics.

Physical, psychological, and social aspects of quality of life in filarial lymphedema patients in Colombo, Sri Lanka.

Quality of life (QOL) was assessed in 141 filarial lymphedema patients and 128 healthy people in the Colombo district, Sri Lanka, by administering modified, translated, and validated (in Sri Lanka) versions of the Short Form 36 health survey questionnaire (SF-36) and the 30-item General Health questionnaire (GHQ-30). The GHQ-30 assesses the current mental health status. The SF-36 measures health on 8 multi-item dimensions covering functional state, well-being, and overall evaluation of health (physical functioning, role limitations resulting from physical health problems, role limitations resulting from emotional problems, energy/fatigue, emotional well-being, social functioning, pain and general health). By SF-36, patients experienced poorer physical functioning, more role limitations resulting from physical health conditions, less emotional well-being, poorer social functioning, and more pain than healthy individuals. By GHQ-30, mental well-being of healthy controls was significantly better than that of patients. The significant difference in the QOL as perceived by filarial lymphedema patients and healthy individuals reiterates the importance of morbidity control in patients affected by this disease.

Host immunity as a determinant of treatment outcome in Plasmodium falciparum malaria.

Host immunity is an important but poorly understood determinant of antimalarial efficacy, influencing the outcome of prevention and treatment trials. Variations in host immunity might explain why factors such as host genetics, age, pregnancy, infection with HIV, parasite density, and malaria transmission intensity, can raise or lower apparent cure rates. Recently, attempts have been made to characterise immunological correlates of treatment outcome in Plasmodium falciparum malaria, but not yet for Plasmodium vivax. A better understanding of such correlates might improve trials of antimalarial drugs and provide leads for vaccine development. Greater understanding of the relation between host immunity and treatment outcome is crucial to making informed choices about the use of safe but partly effective drugs for malaria prevention in children and pregnant women. With increasing malaria control efforts worldwide, declining population immunity might alter drug response profiles. Improved methods for assessing antimalarial immunity will strengthen malaria control efforts.

Treatment-seeking behavior and treatment practices of lymphatic filariasis patients with lymphoedema in the Colombo district, Sri Lanka.

This cross-sectional, descriptive study describes the treatment-seeking behavior of 413 lymphoedema patients attending 2 filariasis clinics in the Colombo district, Sri Lanka. A pretested, interviewer-administered questionnaire obtained information regarding sources and types of treatment taken, time taken for diagnosis, and details regarding diethylcarbamazine citrate (DEC) treatment. There was a mean delay of 2.37 years (SD 1.37) in diagnosing filariasis after the first appearance of limb swelling. General practitioners were the most frequent first-contact health care providers and the most visited source overall, followed by government hospitals and Ayurvedic practitioners. Approximately 95% of patients were on DEC treatment ranging from 10 days to 43 years (mean 2.5 years SD +/- 1.1). Sixty-one percent of patients reported always having taken the recommended DEC course. Nonsteroidal anti-inflammatory drugs, diuretics, and antibiotics were liberally prescribed. Approximately 97% had sought treatment from a medical practitioner for an acute adenolymphangitis attack. Despite the area being endemic for filariasis, there was a delay in treatment and inappropriate use of DEC in patients with chronic filarial lymphoedema.