Evaluation of the Global Fund-supported National Malaria Control Program in Papua New Guinea, 2009-2014

@#The Global Fund to Fight AIDS, Tuberculosis and Malaria is the major funaer of the National Malaria Control Program in Papua New Guinea (PNG). One of the requirements of a Global Fund grant is the regular and accurate reporting of program outcomes and impact. Under-performance as well as failure to report can result in reduction or discontinuation of program funding. While national information systems should be in a position to provide accurate and comprehensive information for program evaluation, systems in developing countries are often insufficient. This paper describes the five-year plan for the evaluation of the Global Fund Round 8 malaria grant to PNG (2009-2014) developed by the Papua New Guinea Institute of Medical Research (PNGIMR). It builds on a complementary set of studies including national surveys and sentinel site surveillance for the assessment of program outcomes and impact. The PNGIMR evaluation plan is an integral part of the Global Fund grant. The evaluation program assesses intervention coverage (at individual, household and health facility levels), antimalarial drug efficacy, indicators of malaria transmission and morbidity (prevalence, incidence), and all-cause mortality. Operational research studies generate complementary information for improving the control program. Through the evaluation, PNGIMR provides scientific expertise to the PNG National Malaria Control Program and contributes to building local capacity in monitoring and evaluation. While a better integration of evaluation activities into routine systems would be desirable, it is unlikely that sufficient capacity for data analysis and reporting could be established at the National Department of Health (NDoH) within a short period of time. Long-term approaches should aim at strengthening the national health information system and building sufficient capacity at NDoH for routine analysis and reporting, while more complex scientific tasks can be supported by the PNGIMR as the de facto research arm of NDoH.

Glycophorin C delta(exon3) is not associated with protection against severe anaemia in Papua New Guinea.

The high frequencies of mutant haemoglobin and erythrocyte surface proteins in malaria-endemic regions have indicated that polymorphisms in human genes have been under selection pressure by severe malarial disease. Glycophorin C (GYPC) is a major surface erythrocyte protein and also a receptor for the Plasmodium falciparum erythrocyte-binding antigen 140 (EBA-140, also known as BAEBL). There is no binding to GYPC in Gerbich-negative (deletion of exon 3 in GYPC gene: GYPCC delta(exon3)) erythrocytes by EBA-140, hence limiting invasion of erythrocytes by certain P. falciparum lines. The GYPCC delta(exon3) allele reaches high frequencies in two areas of Papua New Guinea (PNG) where malaria is highly endemic. There is, however, no indication that Gerbich negativity protects against malaria-related illness. Using archival blood samples collected from children (<6 years of age) in the Wosera District, East Sepik Province, PNG, we investigated GYPC C delta(exon3) as a possible genetic component of protection against severe malarial anaemia (SMA). The frequency of this human genetic polymorphism was found to be in accordance with previous studies. However, our result showed no association between SMA and GYPC C delta(exon3). Until such an association is clearly shown with severe malaria outcomes, these results raise questions regarding the role of malaria as a selective force for Gerbich negativity.

Impact of untreated bednets on prevalence of Wuchereria bancrofti transmitted by Anopheles farauti in Papua New Guinea.

Despite the growing evidence that insecticide-treated mosquito nets reduce malaria morbidity and mortality in a variety of epidemiological conditions, their value against lymphatic filariasis infection and disease is yet to be established. The impact of untreated bednets on the prevalence of Wuchereria bancrofti (Cobbold) (Nematoda: Filarioidea) infection and disease was investigated on Bagabag island in Papua New Guinea, where both malaria and filariasis are transmitted by the same vector mosquitoes of the Anopheles punctulatus Dönitz group (Diptera: Culicidae). Community-wide surveys were conducted recording demographic characteristics including bednet usage. Physical examinations for hydrocoele and lymphoedema were performed and blood samples assessed for filarial and malaria parasites. Mosquitoes were sampled using the all-night landing catch method and individually dissected to determine W. bancrofti infection and infective rates. Bednet usage among residents was 61% and the mean age of users (25.6 years) was similar to non-users (22.5 years). Anopheles farauti Laveran was the only species were found to contain filarial larvae: 2.7% infected (all stages), 0.5% infective (L3). The overall W. bancrofti microfilaraemia and antigenaemia rates were 28.5% and 53.1%, respectively. Bednet users had lower prevalence of W. bancrofti microfilaraemia, antigenaemia and hydrocoele rates than non-users. In comparison, untreated bednets had no effect on the prevalence and intensity of Plasmodium falciparum and P. vivax infections. The impact of bednet usage on rates of microfilaraemia and antigenaemia remained significant even when confounding factors such as age, location and sex were taken into account, suggesting that untreated bednets protect against W. bancrofti infection.

The use of the polymerase chain reaction for more sensitive detection of Plasmodium falciparum.

The prevalence of Plasmodium falciparum in children and adults living in a malaria-endemic area in Papua New Guinea was determined by microscopy and by polymerase chain reaction (PCR). The sensitivity of detecting P. falciparum infections increased two-fold with PCR. Undetected infections by microscopy were more frequent in adults (including adolescents) than in children. Detecting this subpatent parasitaemia by PCR resulted in an equal P. falciparum prevalence in children and adults; in children the parasitaemia rate increased from 32% to 48% and in adults from 23% to 47%. In more than 50% of all blood samples positive for P. vivax and P. malariae an underlying P. falciparum infection remained undetected by microscopy. The introduction of PCR has opened up new possibilities in malaria diagnosis and research.

Assessment of the humoral and cell-mediated immunity against the Plasmodium falciparum vaccine candidates circumsporozoite protein and SPf66 in adults living in highly endemic malarious areas of Papua New Guinea.

To assess natural immunity against the circumsporozoite (CS) protein and the synthetic vaccine SPf66, immunologic studies were carried out in a highly endemic malarious area of Papua New Guinea. Antibody prevalence, antibody titers, and T cell proliferation against both antigens were measured in 214 adults. Immunologic data were analyzed with respect to longitudinal malariologic and morbidity data. Evidence of genetic traits such as glucose-6-phosphate dehydrogenase deficiency and ovalocytosis was analyzed. Antibody prevalence was high, with 79% and 84% for CS protein and SPf66, respectively, while T cell proliferation was infrequent and low, with 14% and 12% responders, respectively. Anti-CS protein antibodies increased with age but showed no association to malaria indices or morbidity. No protective value was observed with T cell responses or with humoral response to SPf66. These results provide a first description of naturally developed immunity against SPf66 and suggest further studies in to fully understand the mechanism of immunity against this antigen.

Plasmodium falciparum: extensive polymorphism in merozoite surface antigen 2 alleles in an area with endemic malaria in Papua New Guinea.

Plasmodium falciparum: Extensive polymorphism in merozoite surface antigen 2 alleles in an area with endemic malaria in Papua New Guinea. Experimental Parasitology 79, 106-116. The prevalence of Plasmodium falciparum in 304 individuals from two villages in Papua New Guinea has been determined by PCR amplification of the gene encoding the merozoite surface antigen 2 (MSA2). Forty-seven percent of the blood samples were positive for P. falciparum. The MSA2 alleles of this parasite population were characterized by PCR-RFLP genotyping. In 144 P. falciparum infections 38 different MSA2 alleles were found. The most common allele (22%) was a variant of FC27. Further alleles, found in the study area, were IC1, KF1916, and MAD71. In addition to these previously described alleles, 33 novel variant forms of MSA2 were detected, most of which were represented at very low frequency in the study population. MSA2 genotyping of a local P. falciparum population revealed an unexpected amount of genetic heterogeneity. The diversity is mostly due to variation in the repeat region resulting in length polymorphism that can be easily detected by PCR-RFLP.

Dynamics of malaria parasitaemia associated with febrile illness in children from a rural area of Madang, Papua New Guinea.

Active community and self-reporting surveillance techniques have been used to describe the dynamics of febrile illness and associated malaria infection in children aged 2 to 15 years from a rural area of Madang Province, Papua New Guinea (PNG). Both history of fever and fever in association with parasitaemia appeared to be reliable indicators of malaria morbidity in this endemic area. Parasite density was observed to be a major determinant of mild malarial disease at both the population level and within an individual. Age-specific prevalence of febrile illness correlated with age-specific patterns of parasite density but not of parasite prevalence. Seasonal changes in fever incidence correlated with parasite density. The transition from afebrile to febrile state within an individual was generally associated with an increase in parasite density. Surveillance and self-reported febrile cases (which differ in severity on the basis of the perceived need for treatment) could be distinguished on the basis of parasite density. Thus surveillance techniques divide clinical malaria in rural PNG into 'mild' and 'very mild' forms. The age-specific pattern of decline of prevalence of malaria-associated febrile illness and parasite density is best explained by induction of strain-specific anti-disease immunity upon infection with a given strain of Plasmodium falciparum. The fever threshold in self-reporting febrile cases was seen to decrease with age and can be explained by an age-specific decline in anti-toxic immunity.