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BACKGROUND: Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia. METHODS: Individual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall ≥ 25% at day 3 and day 7. RESULTS: A total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0-19.7 g/dL) in Africa, 11.6 g/dL (range 5.0-20.0 g/dL) in Asia and 12.3 g/dL (range 6.9-17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to ≥ 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.78 and AOR = 1.

BACKGROUND: Most malarious countries outside of Africa are co-endemic for Plasmodium falciparum and Plasmodium vivax. The comparative burden of anaemia in the community caused by these two species is incompletely characterized. METHODS: A three-stage, cross-sectional, community survey was used to determine the proportion of moderate or severe anaemia (haemoglobin <7 g/dL) attributable to patent P. vivax, P. falciparum and mixed parasitaemia in Papua, Indonesia. Adjusted population-attributable fractions were calculated from multivariable logistic regression models. Eight hundred and twenty-five households were surveyed with a total of 5255 occupants, 3890 (74 %) of whom were present and provided a blood sample. Plasmodium falciparum parasitaemia was present in 8.1 % (n = 315) of participants, P. vivax in 6.4 % (n = 250) and mixed infections in 1.9 % (n = 72). Overall, P. falciparum was associated with a mean reduction in haemoglobin of 1.16 g/dL compared to those without patent parasitaemia [95 % confidence interval (95 % CI) 0.91, 1.41 g/dL]. The corresponding values for P. vivax and mixed infections were 0.66 g/dL (95 % CI 0.35, 0.96) and 1.25 g/dL (0.71, 1.80), respectively. Overall, 16.7 % (95 % CI 8.52, 24.2 %) of haemoglobin concentrations <7 g/dL in the community were estimated to be attributable to patent parasitaemia. The fractions for infants and 1-5 years old were 34.4 % (95 % CI -3.30, 58.3 %) and 23.2 % (95 % CI 3.34, 39.0 %), respectively. Plasmodium vivax was associated with a greater than threefold higher attributable fraction of anaemia in infants compared with P. falciparum [27.6 % (95 % CI -3.20, 49.2 %) versus 7.94 % (-5.87, 20.0 %)]. CONCLUSION: Despite comparatively low-level endemicity, malaria is associated with a significant proportion of all cases of community anaemia in southern Papua. Contrary to its benign reputation, P. vivax is an important and preventable risk factor for anaemia during infancy-a probable consequence of relapsing disea

BACKGROUND: Malaria remains a significant public health issue in Eastern Indonesia, where multidrug resistant Plasmodium falciparum and Plasmodium vivax are highly prevalent. The objective of this study was to describe treatment-seeking behaviour and household costs prior to a change to a unified treatment policy of dihydroartemisinin-piperaquine in Mimika district, Papua province in 2006. METHODS: In 2005 a randomized cross-sectional household survey was conducted to collect data on demographics, socio-economic status (SES), treatment-seeking, case management, and household costs. Information on the cost of illness was also collected from patients exiting health facilities, in order to compare the cost of episodes diagnosed as P. vivax compared with those diagnosed as P. falciparum. RESULTS: 825 households were included in the survey. Of the 764 individuals who sought treatment for fever outside the home in the last month, 46% (349/764) went to a public health facility. Of the 894 reported visits to healthcare providers, 48% (433) resulted in a blood test, of which 78% (337) were reportedly positive. Only 10% (17/177) of individuals who reported testing positive for P. falciparum or mixed infection received the first-line treatment of chloroquine with SP, and 38% (61/159) of those with a diagnosis of P. vivax reportedly received the first-line treatment of chloroquine and primaquine. Overall, public facilities were more likely to prescribe the correct prevailing first-line drug combinations than private providers (OR = 3.77 [95% CI 2.31-6.14], p < 0.001). The mean cost to the household of an episode of P. vivax was similar to the cost of P. falciparum [US$44.50 (SD: 46.23) vs US$48.58 (SD: 64.65)]. CONCLUSIONS: Private providers were a popular source of treatment for malaria, but adherence to the national guidelines was low and the economic burden of malaria for both P. falciparum and P. vivax infections was substantial. Engagement with the private sector is needed

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Results

Weight gain achieved during pulmonary tuberculosis (PTB) treatment is associated with the likelihood of bacteriological treatment success. It is recognised that weight and body mass index (BMI) characteristics differ between ethnic groups in health and illness states. However there has been no prior investigation of how ethnic differences in BMI might influence tuberculosis treatment outcome. Our aim was to investigate predictors of microbiological response to PTB treatment at the Tuberculosis Clinic in Timika, Papua Province, Indonesia and specifically, to determine the contribution of ethnicity. The population comprises two distinct ethnic groups - Asian (Non-Papuan) and Melanesian (Papuan). We conducted a prospective study of adults with smear-positive PTB. Treatment outcomes were 1- and 2-month sputum culture and time to microscopy conversion. Clinical measures included weight, BMI, chest radiograph, pulmonary function including forced expiratory volume in 1 second (FEV1) and haemoglobin. One hundred eighty six participants (83 Papuan, 103 non-Papuan Indonesians) were enrolled. At baseline, Papuans had higher mean weight and BMI than non-Papuans (50.0 kg versus 46.9 kg, p = 0.006 and 20.0 kg/m2 versus 18.7 kg/m2, p = 0.001 respectively). This was despite having lower mean haemoglobin (11.3 vs 13.1 g/dL, p<0.0001), higher smoking and HIV rates (37% vs 21%, p = 0.02 and 20% vs 5%, p = 0.01 respectively) and longer median illness duration (3 vs 2 months, p = 0.04), but similar radiological severity (proportion with cavities 55% vs 57%, p = 0.7), sputum smear grade (p = 0.3) and mean % predicted FEV1 (63% vs 64%, p = 0.7). By 2 months, Papuans had gained still more weight (mean 5.9 vs 4.2 kg, p = 0.02), and were more likely to have negative sputum culture (49/56 vs 45/67, p = 0.02), in univariable and multivariable analyses controlling for other likely determinants of culture conversion. In conclusion, Papuans had better early microbiological outcome from PTB treatm

BACKGROUND: Vitamin D (vitD) and L-arginine have important antimycobacterial effects in humans. Adjunctive therapy with these agents has the potential to improve outcomes in active tuberculosis (TB). METHODS: In a 4-arm randomised, double-blind, placebo-controlled factorial trial in adults with smear-positive pulmonary tuberculosis (PTB) in Timika, Indonesia, we tested the effect of oral adjunctive vitD 50,000 IU 4-weekly or matching placebo, and L-arginine 6.0 g daily or matching placebo, for 8 weeks, on proportions of participants with negative 4-week sputum culture, and on an 8-week clinical score (weight, FEV1, cough, sputum, haemoptysis). All participants with available endpoints were included in analyses according to the study arm to which they were originally assigned. Adults with new smear-positive PTB were eligible. The trial was registered at ClinicalTrials.gov NCT00677339. RESULTS: 200 participants were enrolled, less than the intended sample size: 50 received L-arginine + active vitD, 49 received L-arginine + placebo vit D, 51 received placebo L-arginine + active vitD and 50 received placebo L-arginine + placebo vitD. According to the factorial model, 99 people received arginine, 101 placebo arginine, 101 vitamin D, 99 placebo vitamin D. Results for the primary endpoints were available in 155 (4-week culture) and 167 (clinical score) participants. Sputum culture conversion was achieved by week 4 in 48/76 (63%) participants in the active L-arginine versus 48/79 (61%) in placebo L-arginine arms (risk difference -3%, 95% CI -19 to 13%), and in 44/75 (59%) in the active vitD versus 52/80 (65%) in the placebo vitD arms (risk difference 7%, 95% CI -9 to 22%). The mean clinical outcome score also did not differ between study arms. There were no effects of the interventions on adverse event rates including hypercalcaemia, or other secondary outcomes. CONCLUSION: Neither vitD nor L-arginine supplementation, at the doses administered and with the power attained, a

BACKGROUND: In pulmonary tuberculosis (PTB), morbidity during treatment and residual pulmonary disability can be under-estimated. METHODS: Among adults with smear-positive PTB at an outpatient clinic in Papua, Indonesia, we assessed morbidity at baseline and during treatment, and 6-month residual disability, by measuring functional capacity (six-minute walk test [6MWT] and pulmonary function), quality of life (St George's Respiratory Questionnaire [SGRQ]) and Adverse Events ([AE]: new symptoms not present at outset). Results were compared with findings in locally-recruited volunteers. RESULTS: 200 PTB patients and 40 volunteers were enrolled. 6WMT was 497m (interquartile range 460-529) in controls versus 408m (IQR 346-450) in PTB patients at baseline (p<0.0001) and 470m (IQR 418-515) in PTB patients after 6 months (p=0.02 versus controls). SGRQ total score was 0 units (IQR 0-2.9) in controls, versus 36.9 (27.4-52.8) in PTB patients at baseline (p<0.0001) and 4.3 (1.7-8.8) by 6 months (p<0.0001). Mean percentage of predicted FEV1 was 92% (standard deviation 19.9) in controls, versus 63% (19.4) in PTB patients at baseline (p<0.0001) and 71% (17.5) by 6 months (p<0.0001). After 6 months, 27% of TB patients still had at least moderate-severe pulmonary function impairment, and 57% still had respiratory symptoms, despite most achieving 'successful' treatment outcomes, and reporting good quality of life. More-advanced disease at baseline (longer illness duration, worse baseline X-ray) and HIV positivity predicted residual disability. AE at any time during treatment were common: itch 59%, arthralgia 58%, headache 40%, nausea 33%, vomiting 16%. CONCLUSION: We found high 6-month residual pulmonary disability and high AE rates. Although PTB treatment is highly successful, the extent of morbidity during treatment and residual impairment could be overlooked if not specifically sought. Calculations of PTB-related burden of disease should acknowledge that TB-related morbidity does

BACKGROUND: Designing interventions that will reduce transmission of vivax malaria requires knowledge of Plasmodium vivax gametocyte dynamics. METHODS: We analyzed data from a randomized controlled trial in northwestern Thailand and 2 trials in Papua, Indonesia, to identify and compare risk factors for vivax gametocytemia at enrollment and following treatment. RESULTS: A total of 492 patients with P. vivax infections from Thailand and 476 patients (162 with concurrent falciparum parasitemia) from Indonesia were evaluable. Also, 84.3% (415/492) and 66.6% (209/314) of patients with monoinfection were gametocytemic at enrollment, respectively. The ratio of gametocytemia to asexual parasitemia did not differ between acute and recurrent infections (P = .48 in Thailand, P = .08 in Indonesia). High asexual parasitemia was associated with an increased risk of gametocytemia during follow-up in both locations. In Thailand, the cumulative incidence of gametocytemia between day 7 and day 42 following dihydroartemisinin + piperaquine (DHA + PIP) was 6.92% vs 29.1% following chloroquine (P < .001). In Indonesia, the incidence of gametocytemia was 33.6% following artesunate + amodiaquine (AS + AQ), 7.42% following artemether + lumefantrine, and 6.80% following DHA + PIP (P < .001 for DHA + PIP vs AS + AQ). CONCLUSIONS: P. vivax gametocyte carriage mirrors asexual-stage infection. Prevention of relapses, particularly in those with high asexual parasitemia, is likely the most important strategy for interrupting P. vivax transmission.

BACKGROUND: Dihydroartemisinin-piperaquine (DP) is increasingly recommended for antimalarial treatment in many endemic countries; however, concerns have been raised over its potential under dosing in young children. We investigated the influence of different dosing schedules on DP's clinical efficacy. METHODS AND FINDINGS: A systematic search of the literature was conducted to identify all studies published between 1960 and February 2013, in which patients were enrolled and treated with DP. Principal investigators were approached and invited to share individual patient data with the WorldWide Antimalarial Resistance Network (WWARN). Data were pooled using a standardised methodology. Univariable and multivariable risk factors for parasite recrudescence were identified using a Cox's regression model with shared frailty across the study sites. Twenty-four published and two unpublished studies (n = 7,072 patients) were included in the analysis. After correcting for reinfection by parasite genotyping, Kaplan-Meier survival estimates were 97.7% (95% CI 97.3%-98.1%) at day 42 and 97.2% (95% CI 96.7%-97.7%) at day 63. Overall 28.6% (979/3,429) of children aged 1 to 5 years received a total dose of piperaquine below 48 mg/kg (the lower limit recommended by WHO); this risk was 2.3-2.9-fold greater compared to that in the other age groups and was associated with reduced efficacy at day 63 (94.4% [95% CI 92.6%-96.2%], p<0.001). After adjusting for confounding factors, the mg/kg dose of piperaquine was found to be a significant predictor for recrudescence, the risk increasing by 13% (95% CI 5.0%-21%) for every 5 mg/kg decrease in dose; p = 0.002. In a multivariable model increasing the target minimum total dose of piperaquine in children aged 1 to 5 years old from 48 mg/kg to 59 mg/kg would halve the risk of treatment failure and cure at least 95% of patients; such an increment was not associated with gastrointestinal toxicity in the ten studies in which this could be assessed.

BACKGROUND The grading of radiological severity in clinical trials in tuberculosis (TB) remains unstandardised. The aim of this study was to generate and validate a numerical score for grading chest x-ray (CXR) severity and predicting response to treatment in adults with smear-positive pulmonary TB. METHODS At a TB clinic in Papua, Indonesia, serial CXRs were performed at diagnosis, 2 and 6 months in 115 adults with smear-positive pulmonary TB. Radiographic findings predictive of 2-month sputum microscopy status were used to generate a score. The validity of the score was then assessed in a second data set of 139 comparable adults with TB, recruited 4 years later at the same site. Relationships between the CXR score and other measures of TB severity were examined. RESULTS The estimated proportion of lung affected and presence of cavitation, but not cavity size or other radiological findings, significantly predicted outcome and were combined to derive a score given by percentage of lung affected plus 40 if cavitation was present. As well as predicting 2-month outcome, scores were significantly associated with sputum smear grade at diagnosis (p<0.001), body mass index, lung function, haemoglobin, exercise tolerance and quality of life (p<0.02 for each). In the validation data set, baseline CXR score predicted 2-month smear status significantly more accurately than did the proportion of lung affected alone. In both data sets, CXR scores decreased over time (p<0.001). CONCLUSION This simple, validated method for grading CXR severity in adults with smear-positive pulmonary TB correlates with baseline clinical and microbiological severity and response to treatment, and is suitable for use in clinical trials.

BACKGROUND: In areas where malaria is endemic, infants aged <3 months appear to be relatively protected from symptomatic and severe Plasmodium falciparum malaria, but less is known about the effect of Plasmodium vivax infection in this age group. METHODS: To define malaria morbidity in the first year of life in an area where both multidrug-resistant P. falciparum and P. vivax are highly prevalent, data were gathered on all infants attending a referral hospital in Papua, Indonesia, using systematic data forms and hospital computerized records. Additional clinical and laboratory data were prospectively collected from inpatients aged <3 months. RESULTS: From April 2004 through April 2008, 4976 infants were admitted to the hospital, of whom 1560 (31%) had malaria, with infection equally attributable to P. falciparum and P. vivax. The case-fatality rate was similar for inpatients with P. falciparum malaria (13 [2.2%] of 599 inpatients died) and P. vivax malaria (6 [1.0%] of 603 died; P= .161), whereas severe malarial anemia was more prevalent among those with P. vivax malaria (193 [32%] of 605 vs. 144 [24%] of 601; P= .025). Of the 187 infants aged <3 months, 102 (56%) had P. vivax malaria, and 55 (30%) had P. falciparum malaria. In these young infants, infection with P. vivax was associated with a greater risk of severe anemia (odds ratio, 2.4; 95% confidence interval, 1.03-5.91; P= .041) and severe thrombocytopenia (odds ratio, 3.3; 95% confidence interval, 1.07-10.6; P= .036) compared with those who have P. falciparum infection. CONCLUSIONS: P. vivax malaria is a major cause of morbidity in early infancy. Preventive strategies, early diagnosis, and prompt treatment should be initiated in the perinatal period.

SETTING: Tuberculosis treatment clinic in Papua, Indonesia.OBJECTIVE: To document the impact of pulmonary tuberculosis (PTB) on lung function, exercise tolerance and quality of life (QOL).DESIGN: A prospective cohort study of 115 patients with smear-positive PTB followed for 6 months. Demographics, disease history, sputum microbiology, spirometry, 6-minute weight.walk distance (6MWWD) and QOL (modified St George's Respiratory Questionnaire) were measured at diagnosis and at 2 and 6 months. Analysis was restricted to the 69/115 (60%) subjects who attended all follow-up visits.RESULTS: Subjects who attended all visits were less likely than the full cohort to be of Papuan ethnicity (P < 0.05), were more likely to be cured (P < 0.001) and had better lung function at diagnosis (P < 0.05). Significant lung function impairment (forced expiratory volume in 1 second [FEV1] <60% predicted) was found in 27/69 (39%) at diagnosis. Although this fell during treatment (P < 0.01), 17/69 (24.6%) had persisting significant lung function impairment at treatment completion. As lung function recovered, exercise tolerance (6MWWD) rose by 12.3% (P < 0.001) and QOL improved (P < 0.001).CONCLUSION: In a high-burden setting, PTB causes prolonged, significant impairment of lung function, exercise tolerance and QOL. Current measures of disease burden are likely to underestimate the true impact of disease. Earlier diagnosis and disease-modifying treatments may reduce the long-term impact of PTB.

Maturation of Plasmodium falciparum decreases the deformability of infected red blood cells (RBCs), increasing their clearance as they attempt to pass through endothelial slits of the splenic sinus. Previous studies of Plasmodium vivax-infected RBCs led to opposite conclusions with respect to cellular deformability. To resolve this controversy, P. vivax-infected RBCs were passed through a 2-microm microfluidic channel. In contrast to P. falciparum-infected RBCs, mature P. vivax-infected RBCs readily became deformed through 2-microm constrictions. After this extreme deformation, 67% of P. vivax-infected RBCs recovered a normal appearance; however, 15% of uninfected RBCs were destroyed. Results suggest mechanisms for both avoidance of splenic clearance and anemia in vivax malaria.

Adherence of parasitized erythrocytes to activated endothelium causes microvascular obstruction, tissue ischemia, and clinical complications in severe malaria (SM); however, the mechanisms leading to endothelial activation remain unclear. The angiogenic factors, angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF) are modulators of endothelial activation, with Ang-2 release from Weibel–Palade bodies (WPBs) being regulated by endothelial nitric oxide (NO). We explored the relationships between endothelial NO bioavailability, Ang-2, VEGF, tissue perfusion, and clinical outcomes in SM. We measured plasma Ang-2 and VEGF, together with biomarkers of severity from 146 adults with and without SM, in parallel with longitudinal measures of endothelial function by using reactive hyperemia peripheral arterial tonometry (a measure of endothelial NO bioavailability). Regression was used to relate concentrations of Ang-2/VEGF with malaria disease severity, biomarkers of perfusion, endothelial activation, and parasite biomass. The longitudinal relationship between Ang-2 and endothelial function was assessed by using a mixed-effects model. Ang-2 concentrations were elevated in SM and associated with increased venous lactate, plasma intercellular cell adhesion molecule-1 concentrations, parasite biomass, and mortality. In contrast, VEGF concentrations were inversely associated with these biomarkers. Ang-2 concentrations were significantly better predictors of death than venous lactate (P = 0.03). Recovery of endothelial function was associated with falling concentrations of Ang-2. Ang-2 release from endothelial cells with reduced NO bioavailability is likely to contribute to endothelial activation, sequestered parasite biomass, impaired perfusion, and poor outcome in severe falciparum malaria. Agents that improve endothelial NO, reduce WPB exocytosis, and/or antagonize Ang-2 may have therapeutic roles in SM.

BACKGROUND: Severe malaria is characterized by microvascular obstruction, endothelial dysfunction, and reduced levels of L-arginine and nitric oxide (NO). L-Arginine infusion improves endothelial function in moderately severe malaria. Neither the longitudinal course of endothelial dysfunction nor factors associated with recovery have been characterized in severe malaria. METHODS: Endothelial function was measured longitudinally in adults with severe malaria (n = 49) or moderately severe malaria (n = 48) in Indonesia, using reactive hyperemia peripheral arterial tonometry (RH-PAT). In a mixed-effects model, changes in RH-PAT index values in patients with severe malaria were related to changes in parasitemia, lactate, acidosis, and plasma L-arginine concentrations. RESULTS: Among patients with severe malaria, the proportion with endothelial dysfunction fell from 94% (46/49 patients) to 14% (6/42 patients) before discharge or death (P < .001). In severe malaria, the median time to normal endothelial function was 49 h (interquartile range, 20-70 h) after the start of antimalarial therapy. The mean increase in L-arginine concentrations in patients with severe malaria was 11 micromol/L/24 h (95% confidence interval [CI], 9-13 micromol/L/24 h), from a baseline of 49 micromol/L (95% CI, 37-45 micromol/L). Improvement of endothelial function in patients with severe malaria correlated with increasing levels of L-arginine (r = 0.56; P = .008) and decreasing levels of lactate (r = -0.44; P = .001). CONCLUSIONS: Recovery of endothelial function in severe malaria is associated with recovery from hypoargininemia and lactic acidosis. Agents that can improve endothelial NO production and endothelial function, such as L-arginine, may have potential as adjunctive therapy early during the course of severe malaria.

SETTING: A district-level tuberculosis (TB) control programme in Papua Province, Indonesia. OBJECTIVE: To describe a successful partnership between the District Health Department, a private company and non-governmental health care providers. METHODS: Routinely collected surveillance data were analysed. A conceptual model was constructed to describe TB control in the district. Data were compared with the National TB Control Programme (NTP) performance indicators. RESULTS: Funding for the programme's TB clinic is provided by a private company (PT Freeport Indonesia). The NTP provides the policy framework, treatment guidelines and some supplies. TB clinic staff are included in training programmes and the TB laboratory in the provincial quality assurance system. TB clinic staff are responsible for diagnosis, treatment, default tracing, recording and reporting, health education and community mobilisation. The largest proportion of TB patient referrals came from the community hospital (41%). The TB notification rate (311/100000), TB-HIV (human immunodeficiency virus) co-infection (12%) and multidrug-resistant (MDR) TB (2%) are significantly higher in Mimika, but the treatment success rate for smear-positive patients (91%) is similar to Indonesian national figures. CONCLUSIONS: For true progress in attaining the United Nations Millennium Development Goals for TB in Indonesia, innovative local solutions utilising public-private partnerships are essential. The Mimika model is one such solution that should be tested elsewhere.

Background. Antimalarial drug resistance is now well established in both Plasmodium falciparum and Plasmodium vivax. In southern Papua, Indonesia, where both strains of plasmodia coexist, we have been conducting a series of studies to optimize treatment strategies. Methods. We conducted a randomized trial that compared the efficacy and safety of dihydroartemisininpiperaquine (DHP) with artesunate-amodiaquine (AAQ). The primary end point was the overall cumulative parasitological failure rate at day 42. Results. Of the 334 patients in the evaluable patient population, 185 were infected with P. falciparum, 80 were infected with P. vivax, and 69 were infected with both species. The overall parasitological failure rate at day 42 was 45% (95% confidence interval [CI], 36%-53%) for AAQ and 13% (95% CI, 7.2%-19%) for DHP (hazard ratio [HR], 4.3; 95% CI, 2.5-7.2;). Rates of both recrudescence of P. falciparum infection and recurrence P. vivax of P. vivax infection were significantly higher after receipt of AAQ than after receipt of DHP (HR, 3.4 [95% CI, 1.2-9.4] and 4.3 [95% CI, 2.2-8.2], respectively;). By the end of the study, AAQ recipients were 2.95-fold (95% CI, 1.2- to 4.9-fold) more likely to be anemic and 14.5-fold (95% CI, 3.4- to 61-fold) more likely to have carried P. vivax gametocytes. Conclusions. DHP was more effective and better tolerated than AAQ against multidrug-resistant P. falciparum and P. vivax infections. The prolonged therapeutic effect of piperaquine delayed the time to P. falciparum reinfection, decreased the rate of recurrence of P. vivax infection, and reduced the risk of P. vivax gametocyte carriage and anemia.

Chloroquine resistant malaria is a serious problem in Indonesia particularly in Papua. A trial of the existing antimalarial drugs was conducted in Timika, Papua. The objective of the study was to determine the efficacy of cloroquine (CQ) + sulfadoxine-pyrimethamine (SP). Patients with uncomplicated malaria due to Plasmodium falciparum, P. vivax, P. ovale or P. malariae were enrolled and treated with supervised CQ+SP (P. falciparum) or CQ (non-P. falciparum). Patients were followed for 28-42 days. Patients failing therapy were retreated with unsupervised quinine±doxycycline. 207 patients were enrolled in the study (88 P. falciparum, 40 P. vivax, 15 mixed infections, 50 P. malariae and 14 P. ovale). Early treatment failures occurred in 4 of 86 (5%) patients with falciparum malaria, 6 of 37 (16%) patients with vivax malaria and none of those with P. ovale or P. malariae infections. The failure rate by day 28 for P. vivax was 22 of 30 (73%) patients, with all recurrences occurring in the presence of plasma chloroquine concentration above the minimum effective concentration (MEC>15ng/ml). After correcting for reinfections the day 42 recrudescence rate for falciparum malaria was 48% [95%CI:31-65] and in 61% of cases this was in the presence of chloroquine levels above 30 ng/ml. Retreatment with unsupervised quinine±doxycycline resulted in further recurrence of malaria in 48% [95%CI:31-65] of P. falciparum infections and 70% [95%CI:37-100] of P. vivax infections. None of the patients with P. ovale or P. malariae had treatment failures within 28 days. There is a high prevalence of antimalarial drug resistance of P. falciparum and P. vivax to the existing antimalarial drugs. However chloroquine retains adequate efficacy against P. ovale and P. malariae in Papua. (Med J Indones 2006; 15:251-8)

SETTING: A district level tuberculosis (TB) control programme in Papua Province, Indonesia.OBJECTIVE: To determine the nature and extent of drug-resistant TB in newly diagnosed sputum smear-positive patients.METHODS: Sputum was collected from previously untreated smear-positive pulmonary TB patients diagnosed in the district over a 10-month period. Sputum specimens were processed and inoculated into a BACTEC MGIT960 tube. Isolates were identified by Ziehl-Neelsen staining, hybridisation with nucleic acid probes and biochemical investigations. Susceptibility testing was performed using the radiometric proportion method. Pyrazinamide testing was performed using the Wayne indirect method.RESULTS: One hundred and seven patients had sputum sent to a reference laboratory; 101 (94.4%) were culture-positive for Mycobacterium tuberculosis, with 87 (86.1%) fully sensitive to first-line anti-tuberculosis drugs. Two per cent were multidrug-resistant (MDR-TB) and 12 (11.9%) had other drug resistance. Each of the MDR-TB isolates was susceptible to amikacin, capreomycin, ciprofloxacin and para-aminosalicylic acid (PAS), but were resistant to rifabutin. One isolate was also resistant to ethionamide.CONCLUSIONS: MDR-TB is present in Indonesia but is not a major problem for TB control in this district. Generalisability to other districts in Indonesia, particularly large urban areas, needs to be confirmed by future studies.