Haematological profile of children with malaria in Sorong, West Papua, Indonesia.

BACKGROUND: Malaria remains a major public health problem in Indonesian Papua, with children under five years of age being the most affected group. Haematological changes, such as cytopenia that occur during malaria infection have been suggested as potential predictors and can aid in the diagnosis of malaria. This study aimed to assess the haematological alterations associated with malaria infection in children presenting with signs and symptoms of malaria. METHODS: A retrospective study was performed by collecting data from the medical records of malaria patients at Sorong Regional General Hospital, Sorong, West Papua, Indonesia, both from outpatient and inpatient clinics, from January 2014 until December 2017. The laboratory profile of children suffering from malaria was evaluated. RESULTS: One hundred and eighty-two children aged 1 month to 18 years old were enrolled. The subjects were mostly male (112, 61.5%) with a mean age of 6.45 years (SD = 4.3 years). Children below 5 years of age suffered the most from malaria in this study (77, 42.3%). One hundred two subjects (56%) were infected with Plasmodium falciparum. Half of the enrolled subjects (50%) had haemoglobin level (Hb) between 5.1 and 10 gr/dL. A total of 41 children (53.2%) less than 5 years old suffered from P. falciparum infection. In the age group of 5-10 years, there were 34 children (57.6%) who suffered from P. falciparum, and in the age group > 10 years, 27 children (58.7%) suffered from P. falciparum infection. Only 4 subjects (5.2%) in the less than 5 years old age group had mixed malaria infection. Among eight predictors of the haematological profile, there were five predictors that were significantly associated with the diagnostic criteria, namely haemoglobin, haematocrit, leukocytes, platelets and monocytes (p < 0.05). Generally, clinical symptoms are not significantly associated with a malaria diagnosis, and only one variable showed a significant relationship, pale, with a P value of 0.001. CONCLUSIONS: Children with malaria had changes in some haematological markers, with anaemia, low platelet count, white blood count, and lymphocyte count being the most important predictors of malaria infection in the study area. These markers could be used to raise suspicion of malaria in children living in high endemic areas, such as West Papua.

Individual and contextual factors predicting self-reported malaria among adults in eastern Indonesia: findings from Indonesian community-based survey.

BACKGROUND: Malaria is still an important parasitic infectious disease that affecting poor and vulnerable communities in many developing countries, including Indonesia. During the period of 2010-2017, there have been approximately 2.2 million confirmed malaria cases reported across Indonesia. This study aimed to identify individual, household and village-level factors associated with self-reported malaria among adults more than 15 years of age in Maluku, West Papua and Papua province. METHODS: This study analysed a subset of the data from nationally representative population-based Indonesian National Basic Health Research (Riset Kesehatan Dasar) (N = 1,027,763 in 294,959 households in 33 provinces) in 2013. Total of 41,079 individuals (20,326 males and 20,753 females) aged ≥ 15 years in 19,269 households in Maluku, West Papua and Papua provinces were included. Participants were interviewed if they ever had been diagnosed and laboratory confirmed of having malaria by physician in the past 12 months. A mixed effects multilevel logistic regression models were developed to assess the associations between socio-demographical variables at individual, household and village level and self-reported malaria. RESULTS: Individuals aged ≥ 15 years in 701 villages in Maluku (n = 11,919), West Papua (n = 8003) and Papua (n = 21,157) were analysed. In all provinces, gender distribution was equally-represented. The prevalence of self-reported malaria was 4.1% (Maluku), 12.4% (West Papua) and 18.8% (Papua). At the individual level, primary industry workers (OR 1.29, 95% CI 1.15-1.46 [Maluku]; OR 1.17, 95% CI 1.09-1.25 [Papua]) and having higher education were associated with self-reporting malaria (OR 0.67, 95% CI 0.53-0.83 [Maluku]; OR 1.27, 95% CI 1.15-1.40 [Papua]). Household level factors include having bed net and better off wealth index were associated with increased self-reporting malaria among West Papua (OR 1.21; 95% CI 1.09-1.34 and OR 1.38; 95% CI 1.17-1.65, respectively) and Papuan (OR 1.12; 95% CI 1.02-1.23 and OR 1.33; 95% CI 1.11-1.57, respectively) adults. Increased odds of self-reporting malaria was associated with time required to reach healthcare facility (OR 1.30, 95% CI 1.01-1.67 [Maluku]). Contextual village-level characteristics such as living in rural (OR 1.31, 95% CI 1.12-1.54 [Maluku]; OR 1.56, 95% CI 1.17-2.07 [West Papua]), higher community education level (OR 1.28, 95% CI 1.02-1.63 [West Papua]; OR 1.45, 95% CI 1.23-1.72 [Papua]), higher community bed net ownerships (OR 0.59 95% CI 0.45-0.77 [West Papua]) were associated with self-reported malaria. CONCLUSIONS: Factors associated with self-reported malaria were varied between provinces suggesting locally-specific determinants were exist at individual, household and community-level. This study highlights the need for specific interventions by taking into consideration the contextual factors within the region and involving multi-sectoral collaboration between health authorities and related stakeholders (e.g., bureau of education, bureau of public works and infrastructure) to improve designs in planning and intervention strategies to succesfully eliminate malaria in Maluku and Papua.

Strategies to reduce and maintain low perinatal mortality in resource-poor settings - Findings from a four-decade observational study of birth records from a large public maternity hospital in Papua New Guinea.

BACKGROUND: In many low- to middle-income countries (LMIC) assisted vaginal birth rates have fallen, while caesarean section (CS) rates have increased, with potentially deleterious consequences for maternal and perinatal mortality. AIMS: To review birth mode and perinatal mortality in a large LMIC hospital with strict labour management protocols and expertise in vacuum extraction. MATERIALS AND METHODS: We conducted a retrospective observational study at Port Moresby General Hospital in Papua New Guinea. Birth registers from 1977 to 2015 (39 years) were reviewed. Overall and modified (fresh stillbirths and early neonatal deaths ≥500 g) perinatal mortality rates (PMRs) were calculated by birthweight/birth mode. RESULTS: There were 365 056 births (5215 in 1977; 14 927 in 2015), of which 14 179 (3.9%) were vacuum extractions, 609 (0.2%) forceps births and 14 747 (4.4%) CS (increase from 2% to 5%). The failure rate of vacuum extraction was 2.5% (range 0.5-5.4%). Symphysiotomy was employed for 184 births. From 1989 to 2015, the modified mean PMR for babies ≥2500 g was 8.1/1000 births (range 5.6-12.1; 6.9 in 2015), 9.1/1000 for babies ≥1500 g (7.3-14.8; 9.1 in 2015) and 7.5/1000 (0-21.7; 9.0 in 2015) for vacuum extractions (98% were ≥2500 g). The overall PMR for these years was 29.7/1000 births. CONCLUSIONS: In an LMIC with rapidly increasing birth numbers a comparatively low PMR can be achieved while maintaining low CS rates. This may be in part accomplished through strict use of second-stage protocols, perinatal audit, and supportive training that promotes judicious and proficient use of vacuum extraction and CS.

Defining a combined constellation of complicated bereavement and PTSD and the psychosocial correlates associated with the pattern amongst refugees from West Papua.

BACKGROUND: Refugees are at risk of experiencing a combined constellation of complicated bereavement and posttraumatic stress disorder (PTSD) symptoms following exposure to complex traumas associated with personal threat and loss. Features of identity confusion are central to both complicated bereavement and PTSD and these characteristics may be particularly prominent amongst refugees from traditional cultures displaced from their homelands, families, and kinship groups. We investigate whether a combined pattern of complicated bereavement and PTSD can be identified amongst West Papuan refugees participating in an epidemiological survey (n = 486, response rate: 85.8%) in a remote town in Papua New Guinea. METHODS: Latent class analysis was applied to derive subpopulations of refugees based on symptoms of complicated bereavement and PTSD. Associations were examined between classes and traumatic loss events, post-migration living difficulties (PMLDs), and psychosocial support systems. RESULTS: The four classes identified comprised a complicated bereavement class (11%), a combined posttraumatic bereavement class (10%), a PTSD class (11%), and a low symptom class (67%). Symptoms of identity confusion were prominent in the posttraumatic bereavement class. Compared with the low symptom class, the combined posttraumatic bereavement class reported greater exposure to traumatic loss events (OR 2.43, 95% CI 1.11-5.34), PMLDs (OR 2.24, 95% CI 1.01-4.6), disruptions to interpersonal bonds and networks (OR 3.3, 95% CI 1.47-7.38), and erosion of roles and identities (OR 2.18, 95% CI 1.11-4.27). CONCLUSIONS: Refugees appear to manifest a combined pattern of complicated bereavement and PTSD symptoms in which identity confusion is a prominent feature. This response appears to reflect the combined impact of high levels of exposure to traumatic losses, PMLDs, and disruption of relevant psychosocial systems.

Increasingly inbred and fragmented populations of Plasmodium vivax associated with the eastward decline in malaria transmission across the Southwest Pacific.

The human malaria parasite Plasmodium vivax is more resistant to malaria control strategies than Plasmodium falciparum, and maintains high genetic diversity even when transmission is low. To investigate whether declining P. vivax transmission leads to increasing population structure that would facilitate elimination, we genotyped samples from across the Southwest Pacific region, which experiences an eastward decline in malaria transmission, as well as samples from two time points at one site (Tetere, Solomon Islands) during intensified malaria control. Analysis of 887 P. vivax microsatellite haplotypes from hyperendemic Papua New Guinea (PNG, n = 443), meso-hyperendemic Solomon Islands (n = 420), and hypoendemic Vanuatu (n = 24) revealed increasing population structure and multilocus linkage disequilibrium yet a modest decline in diversity as transmission decreases over space and time. In Solomon Islands, which has had sustained control efforts for 20 years, and Vanuatu, which has experienced sustained low transmission for many years, significant population structure was observed at different spatial scales. We conclude that control efforts will eventually impact P. vivax population structure and with sustained pressure, populations may eventually fragment into a limited number of clustered foci that could be targeted for elimination.

Joint Modeling of Mixed Plasmodium Species Infections Using a Bivariate Poisson Lognormal Model.

Infectious diseases often present as coinfections that may affect each other in positive or negative ways. Understanding the relationship between two coinfecting pathogens is thus important to understand the risk of infection and burden of disease caused by each pathogen. Although coinfections with Plasmodium falciparum and Plasmodium vivax are very common outside Africa, it is yet unclear whether infections by the two parasite species are positively associated or if infection by one parasite suppresses the other. In this study, we use bivariate Poisson lognormal models (BPLM) to estimate covariate-adjusted associations between the incidence of infections (as measured by the force of blood-stage infections, molFOI) and clinical episodes caused by both P. falciparum and P. vivax in a cohort of Papua New Guinean children. A BPLM permits estimation of either positive or negative correlation, unlike most other multivariate Poisson models. Our results demonstrated a moderately positive association between P. falciparum and P. vivax infection rates, arguing against the hypothesis that P. vivax infections protect against P. falciparum infections. Our findings also suggest that the BPLM is only useful for counts with suitably large means and overdispersion.

The Multifactorial Epidemiology of Blackwater Fever.

Blackwater fever is a massive hemolytic event usually occurring in the context of repeated falciparum malaria infections and intermittent quinine use. Its etiology is poorly understood, and it is rarely seen today. Historical epidemiological observations from the 20th century demonstrated variable patterns in prisoners in Andaman Islands, refugees in Macedonia, canal workers in Panama, expatriates in Rhodesia, and Second World War soldiers. Rates of blackwater fever per 1,000 malaria cases varied over two orders of magnitude. Islands, such as the Andaman Islands and New Guinea, had lower blackwater fever rates than continental areas. During the Second World War, blackwater fever rates in British soldiers in West Africa and Australian soldiers in New Guinea differed by a factor of 40 despite similar treatment regimens and falciparum malaria transmission risks. Blackwater fever is a complex interaction between host erythrocyte, falciparum malaria, and antimalarial drugs which remains poorly understood.

Detection of enteric viral and bacterial pathogens associated with paediatric diarrhoea in Goroka, Papua New Guinea.

OBJECTIVES: The aim of this study was to investigate the viral and bacterial causes of acute watery diarrhoea in hospitalized children in Papua New Guinea. METHODS: A retrospective analysis was conducted on stool samples collected from 199 children (age <5 years) admitted to the paediatric ward of Goroka General Hospital from August 2009 through November 2010. A large range of viral and bacterial enteric pathogens were targeted using real-time PCR/RT-PCR assays. RESULTS: Young children were much more likely to be admitted with acute gastroenteritis, with 62.8% of patients aged <1 year and 88.4% aged <2 years. An enteric pathogen was detected in 69.8% (n=138) of patients. The most commonly detected pathogens were Shigella spp (26.6%), rotavirus (25.6%), adenovirus types 40/41 (11.6%), enterotoxigenic Escherichia coli (11.1%), enteropathogenic E. coli (8.5%), norovirus G2 (6.0%), and Campylobacter spp (4.0%). Norovirus G1, sapovirus, and Salmonella spp were also detected, but below our statistical limit of detection. Vibrio cholerae and astrovirus were not detected in any patients. Mixed infections were detected in 22.1% of patients, with Shigella and rotavirus most commonly detected in co-infections with other pathogens. CONCLUSIONS: This study demonstrates that Shigella and rotavirus are the major pathogens associated with acute paediatric gastroenteritis in this setting.

A high force of plasmodium vivax blood-stage infection drives the rapid acquisition of immunity in papua new guinean children.

BACKGROUND: When both parasite species are co-endemic, Plasmodium vivax incidence peaks in younger children compared to P. falciparum. To identify differences in the number of blood stage infections of these species and its potential link to acquisition of immunity, we have estimated the molecular force of blood-stage infection of P. vivax ((mol)FOB, i.e. the number of genetically distinct blood-stage infections over time), and compared it to previously reported values for P. falciparum. METHODS: P. vivax (mol)FOB was estimated by high resolution genotyping parasites in samples collected over 16 months in a cohort of 264 Papua New Guinean children living in an area highly endemic for P. falciparum and P. vivax. In this cohort, P. vivax episodes decreased three-fold over the age range of 1-4.5 years. RESULTS: On average, children acquired 14.0 new P. vivax blood-stage clones/child/year-at-risk. While the incidence of clinical P. vivax illness was strongly associated with mol FOB (incidence rate ratio (IRR) = 1.99, 95% confidence interval (CI95) [1.80, 2.19]), (mol)FOB did not change with age. The incidence of P. vivax showed a faster decrease with age in children with high (IRR = 0.49, CI95 [0.38, 0.64] p<0.001) compared to those with low exposure (IRR = 0.63, CI95[0.43, 0.93] p = 0.02). CONCLUSION: P. vivax (mol)FOB is considerably higher than P. falciparum (mol)FOB (5.5 clones/child/year-at-risk). The high number of P. vivax clones that infect children in early childhood contribute to the rapid acquisition of immunity against clinical P. vivax malaria.

Neurological damage to the fetus resulting from severe iodine deficiency during pregnancy.

Endemic cretinism is characterised by multiple neurological defects including deaf-mutism, diplegia, squint, and mental deficiency. The condition is widely prevalent in the Highlands of New Guinea in association with severe iodine deficiency. Previous studies have shown that iodised oil provides a very satisfactory correction of severe iodine deficiency in New Guinea. A controlled trial on the use of intramuscular iodised oil in the prevention of endemic cretinism was carried out in the Western Highlands of New Guinea and involved a population of approximately 8000. Subsequent follow-up over four years revealed 26 endemic cretins out of a total of 534 children born to mothers who had not received iodised oil; the mothers of 5 of these cretins were pregnant at the start of the trial. In comparison, 7 cases of endemic cretinism occurred among 498 children born to mothers who had been treated with iodised oil; in 6 of these 7 cases, the mother was pregnant when the trial commenced. It is concluded that intramuscular iodised oil is effective in the prevention of endemic cretinism and that, for it to be effective, it should be given prior to conception. This suggests that severe iodine deficiency in the mother produces neurological damage during fetal development.

Strain-specific duffy binding protein antibodies correlate with protection against infection with homologous compared to heterologous plasmodium vivax strains in Papua New Guinean children.

Individuals repeatedly infected with malaria acquire protection from infection and disease; immunity is thought to be primarily antibody-mediated and directed to blood-stage infection. Merozoite surface proteins involved in the invasion of host erythrocytes are likely targets of protective antibodies. We hypothesized that Papua New Guinean children (n = 206) who acquire high antibody levels to two Plasmodium vivax merozoite proteins, Duffy binding protein region II (PvDBPII) and the 19-kDa C-terminal region of P. vivax merozoite surface protein 1 (PvMSP1(19)), would have a delay in the time to reinfection following treatment to clear all blood-stage malaria infections. Ninety-four percent of the children were reinfected with P. vivax during biweekly follow-ups for 6 months. Since PvDBPII is polymorphic, we examined whether individuals acquired strain-specific immunity to PvDBPII. Children with high antibody levels to a prevalent PvDBPII allele (O) were associated with a delay in the time to reinfection with the same variant of P. vivax by 25% compared to parasites expressing other PvDBPII alleles (age-adjusted hazard ratio, 0.75 [95% confidence interval, 0.56 to 1.00 by Cox regression]) and 39% lower incidence density parasitemia (P = 0.01). Two other prevalent alleles (AH and P) showed a similar trend of 16% and 18% protection, respectively, against parasites with the same PvDBPII allele and reduced incidence density parasitemia. Antibodies directed to PvDBPII PNG-P and -O were both associated with a 21 to 26% reduction in the risk of P. vivax infections with higher levels of parasitemia (>150 parasites/mul), respectively. There was no association with high antibody levels to PvMSP1(19) and a delay in the time to P. vivax reinfection. Thus, anti-PvDBPII antibodies are associated with strain-specific immunity to P. vivax and support the use of PvDBPII for a vaccine against P. vivax.

Is human malarial coma caused, or merely deepened, by sequestration?

Much research into falciparum malaria coma assumes the primary event to be vascular obstruction by parasitized red blood cells. Recent evidence that vivax malaria, caused by a parasite traditionally thought not to block blood flow, seems to alter brain function to the same degree as falciparum malaria has seriously questioned this. These data are a timely call to reassess whether vascular obstruction should still be considered the primary cause of the coma of falciparum disease. They add to a growing literature that suggests that enhancement of brain-origin cytokines, such as tumour necrosis factor, by non-brain systemic inflammation and an appreciation of the degree to which neuronal homeostasis depends on them provide a more fruitful research direction.

Early introduction of solids and pneumonia in young infants in Papua new Guinea: a case control study.

A prospective case control study to determine the association of early introduction of solids with admission to hospital with pneumonia was undertaken at Mount Hagen General Hospital (MHGH) in the highlands of Papua New Guinea (PNG) over a 3-month period in 2005. Twenty three infants up to 6 months of age admitted with radiologically confirmed pneumonia were compared with 24 infants of similar age attending the well baby clinic for immunization and with 35 infants admitted to the hospital with conditions other than pneumonia or meningitis. There was a highly significant difference in feeding patterns between the groups. Children with pneumonia were much more likely than the control children to have started solids before the age of 2 months [OR = 18.06 (4.8-72.86)]. They were also significantly more likely to have been admitted previously with a diagnosis of pneumonia (P < 0.001). The children in each group were of comparable age and weight and there were no obvious confounding factors. This study provides clear evidence for the association between early introduction of solids and pneumonia in PNG highlands children. The findings are consistent with other international data. While the reasons for the association remain speculative, the association strongly reinforces the need to educate the community on best infant feeding practices and to discourage the early introduction of solids.

Serum levels of matrix metalloproteinase-9 and tissue inhibitors of metalloproteinases 1 in subacute sclerosing panencephalitis.

We determined the relationship between the serum concentrations of matrix metalloproteinase-9 (MMP-9) and tissue inhibitors of metalloproteinases 1 (TIMP-1) in 33 patients with subacute sclerosing panencephalitis (SSPE) to investigate the function of the blood-brain-barrier (BBB) in SSPE. Serum MMP-9 and TIMP-1 levels were measured by ELISA. Serum MMP-9 levels and MMP-9/TIMP-1 ratios of SSPE patients in Papua New Guinea (n = 24), and those in Japan (n = 9) were significantly higher than the each control (MMP-9, p = 0.0390, and p = 0.0023, respectively; MMP-9/TIMP-1, p = 0.0319, and p = 0.0009, respectively). Serum MMP-9 levels and MMP-9/TIMP-1 ratios of SSPE patients with Jabbour stage III (n = 13) were significantly higher than those with Jabbour stage II (n = 18) (p = 0.003, and p = 0.0412, respectively). There were no significant differences of serum TIMP-1 levels between the SSPE patients and controls. High serum MMP-9 and MMP-9/TIMP-1 levels will promote brain invasion through the BBB by immunocompetent cells in the blood. Our findings suggest that the balance of serum MMP-9 and TIMP-1 levels modulate the inflammatory cascade of SSPE.

Application of respondent driven sampling to collect baseline data on FSWs and MSM for HIV risk reduction interventions in two urban centres in Papua New Guinea.

The need to obtain unbiased information among hard-to-reach and hidden populations for behavioural and biological surveillance, epidemiological studies, and intervention program evaluations has led researchers to search for a suitable sampling method. One method that has been tested among IDU and MSM recently is respondent-driven sampling (RDS). We used RDS to conduct a behavioural survey among FSWs and MSM in two urban centres in Papua New Guinea (PNG). In this paper we present the lessons learned implementing RDS in a developing country setting. We also present comparisons of RDSAT-adjusted versus unadjusted crude estimates of some key socio-demographic indicators as well as comparisons between the estimates from RDS and a hypothetical time-location sample (TLS). Overall, the use of RDS among the MSM and FSWs in PNG had numerous advantages in terms of collecting a required sample size in a short time period, minimizing costs and maximising security for staff and respondents. Although there were a few problems these were easily remedied and we would recommend RDS for other similar studies in PNG and other developing countries.