Erratum to: Evaluation of a surgical service in the chronic phase of a refugee camp: an example from the Thai-Myanmar border.

[This corrects the article DOI: 10.1186/1752-1505-6-5.].

Pregnancy outcome in relation to treatment of murine typhus and scrub typhus infection: a fever cohort and a case series analysis.

BACKGROUND: There is a paucity of published reports on pregnancy outcome following scrub and murine typhus despite these infections being leading causes of undifferentiated fever in Asia. This study aimed to relate pregnancy outcome with treatment of typhus. METHODOLOGY/PRINCIPAL FINDINGS: Data were analyzed from: i) pregnant women with a diagnosis of scrub and/or murine typhus from a fever cohort studies; ii) case series of published studies in PubMed using the search terms "scrub typhus" (ST), "murine typhus" (MT), "Orientia tsutsugamushi", "Rickettsia tsutsugamushi", "Rickettsia typhi", "rickettsiae", "typhus", or "rickettsiosis"; and "pregnancy", until February 2014 and iii) an unpublished case series. Fever clearance time (FCT) and pregnancy outcome (miscarriage and delivery) were compared to treatment. Poor neonatal outcome was a composite measure for pregnancies sustained to 28 weeks or more of gestation ending in stillbirth, preterm birth, or delivery of a growth restricted or low birth weight newborn. RESULTS: There were 26 women in the fever cohort. MT and ST were clinically indistinguishable apart from two ST patients with eschars. FCTs (median [range] hours) were 25 [16-42] for azithromycin (n=5), 34 [20-53] for antimalarials (n=5) and 92 [6-260] for other antibiotics/supportive therapy (n=16). There were 36.4% (8/22) with a poor neonatal outcome. In 18 years, 97 pregnancies were collated, 82 with known outcomes, including two maternal deaths. Proportions of miscarriage 17.3% (14/81) and poor neonatal outcomes 41.8% (28/67) were high, increasing with longer FCTs (p=0.050, linear trend). Use of azithromycin was not significantly associated with improved neonatal outcomes (p=0.610). CONCLUSION: The published ST and MT world literature amounts to less than 100 pregnancies due to under recognition and under diagnosis. Evidence supporting the most commonly used treatment, azithromycin, is weak. Collaborative, prospective clinical trials in pregnant women are urgently required to reduce the burden of adverse maternal and newborn outcomes and to determine the safety and efficacy of antimicrobial treatment.

Evaluation of a surgical service in the chronic phase of a refugee camp: an example from the Thai-Myanmar border.

BACKGROUND: Published literature on surgical care in refugees tends to focus on the acute ('emergent') phase of crisis situations. Here we posit that there is a substantial burden of non-acute morbidity amenable to surgical intervention among refugees in the 'chronic' phase of crisis situations. We describe surgery for non-acute conditions undertaken at Mae La Refugee Camp, Thailand over a two year period. METHODS: Surgery was performed by a general surgeon in a dedicated room of Mae La Refugee Camp over May 2005 to April 2007 with minimal instruments and staff. We obtained the equivalent costs for these procedures if they were done at the local Thai District General Hospital. We also acquired the list (and costs) of acute surgical referrals to the District General Hospital over September 2006 to December 2007. RESULTS: 855 operations were performed on 847 patients in Mae La Refugee Camp (60.1% sterilizations, 13.3% 'general surgery', 5.6% 'gynaecological surgery', 17.4% 'mass excisions', 3.5% 'other'). These procedures were worth 2,207,500 THB (75,683.33 USD) at costs quoted by the District General Hospital. Total cost encountered for these operations (including staff costs, consumables, anaesthesia and capital costs such as construction) equaled 1,280,000 THB (42,666 USD). Pertaining to acute surgical referrals to District General hospital: we estimate that 356,411.96 THB (11,880.40 USD) worth of operations over 14 months were potentially preventable if these cases had been operated at an earlier, non-acute state in Mae La Refugee Camp. CONCLUSIONS: A considerable burden of non-acute surgical morbidity exists in 'chronic' refugee situations. An in-house general surgical service is found to be cost-effective in relieving some of this burden and should be considered by policy makers as a viable intervention.

Effect of early detection and treatment on malaria related maternal mortality on the north-western border of Thailand 1986-2010.

INTRODUCTION: Maternal mortality is high in developing countries, but there are few data in high-risk groups such as migrants and refugees in malaria-endemic areas. Trends in maternal mortality were followed over 25 years in antenatal clinics prospectively established in an area with low seasonal transmission on the north-western border of Thailand. METHODS AND FINDINGS: All medical records from women who attended the Shoklo Malaria Research Unit antenatal clinics from 12(th) May 1986 to 31(st) December 2010 were reviewed, and maternal death records were analyzed for causality. There were 71 pregnancy-related deaths recorded amongst 50,981 women who attended antenatal care at least once. Three were suicide and excluded from the analysis as incidental deaths. The estimated maternal mortality ratio (MMR) overall was 184 (95%CI 150-230) per 100,000 live births. In camps for displaced persons there has been a six-fold decline in the MMR from 499 (95%CI 200-780) in 1986-90 to 79 (40-170) in 2006-10, p<0.05. In migrants from adjacent Myanmar the decline in MMR was less significant: 588 (100-3260) to 252 (150-430) from 1996-2000 to 2006-2010. Mortality from P. falciparum malaria in pregnancy dropped sharply with the introduction of systematic screening and treatment and continued to decline with the reduction in the incidence of malaria in the communities. P. vivax was not a cause of maternal death in this population. Infection (non-puerperal sepsis and P. falciparum malaria) accounted for 39.7 (27/68) % of all deaths. CONCLUSIONS: Frequent antenatal clinic screening allows early detection and treatment of falciparum malaria and substantially reduces maternal mortality from P. falciparum malaria. No significant decline has been observed in deaths from sepsis or other causes in refugee and migrant women on the Thai-Myanmar border.

Diagnostic and treatment difficulties of pyelonephritis in pregnancy in resource-limited settings.

Limited microbiology services impede adequate diagnosis and treatment of common infections such as pyelonephritis in resource-limited settings. Febrile pregnant women attending antenatal clinics at Shoklo Malaria Research Unit were offered urine dipstick, sediment microscopy, urine culture, and a 5-mL blood culture. The incidence of pyelonephritis was 11/1,000 deliveries (N = 53 in 4,819 pregnancies) between January 7, 2004 and May 17, 2006. Pyelonephritis accounted for 20.2% (41/203) of fever cases in pregnancy. Escherichia coli was the most commonly isolated pathogen: 87.5% (28/32) of organisms cultured. Susceptibility of E. coli to ampicillin (14%), cotrimoxazole (21%), and amoxicillin-clavulanic acid (48%) was very low. E. coli was susceptible to ceftriaxone and ciprofloxacin. The rate of extended spectrum ß-lactamase (4.2%; 95% confidence interval = 0.7-19.5) was low. The rate and causes of pyelonephritis in pregnant refugee and migrant women were comparable with those described in developed countries. Diagnostic innovation in microbiology that permits affordable access is a high priority for resource-poor settings.

Arthropod borne disease: the leading cause of fever in pregnancy on the Thai-Burmese border.

BACKGROUND: Fever in pregnancy is dangerous for both mother and foetus. In the 1980's malaria was the leading cause of death in pregnant women in refugee camps on the Thai-Burmese border. Artemisinin combination therapy has significantly reduced the incidence of malaria in the population. The remaining causes of fever in pregnancy are not well documented. METHODOLOGY: Pregnant women attending antenatal care, where weekly screening for malaria is routine, were invited to have a comprehensive clinical and laboratory screen if they had fever. Women were admitted to hospital, treated and followed up weekly until delivery. A convalescent serum was collected on day 21. Delivery outcomes were recorded. PRINCIPAL FINDINGS: Febrile episodes (n = 438) occurred in 5.0% (409/8,117) of pregnant women attending antenatal clinics from 7-Jan-2004 to 17-May-2006. The main cause was malaria in 55.5% (227/409). A cohort of 203 (49.6% of 409) women had detailed fever investigations and follow up. Arthropod-borne (malaria, rickettsial infections, and dengue) and zoonotic disease (leptospirosis) accounted for nearly half of all febrile illnesses, 47.3% (96/203). Coinfection was observed in 3.9% (8/203) of women, mostly malaria and rickettsia. Pyelonephritis, 19.7% (40/203), was also a common cause of fever. Once malaria, pyelonephritis and acute respiratory illness are excluded by microscopy and/or clinical findings, one-third of the remaining febrile infections will be caused by rickettsia or leptospirosis. Scrub and murine typhus were associated with poor pregnancy outcomes including stillbirth and low birth weight. One woman died (no positive laboratory tests). CONCLUSION/SIGNIFICANCE: Malaria remains the leading cause of fever in pregnancy on the Thai-Burmese border. Scrub and murine typhus were also important causes of fever associated with poor pregnancy outcomes. Febrile pregnant women on the Thai-Burmese border who do not have malaria, pyelonephritis or respiratory tract infection should be treated with azithromycin, effective for typhus and leptospirosis.

Castor oil for induction of labour: not harmful, not helpful.

BACKGROUND: Castor oil is one of the most popular drugs for induction of labour in a non-medical setting; however, published data on safety and effectiveness of this compound to induce labour remain sparse. AIM: To assess the safety and effectiveness of castor oil for induction of labour in pregnancies with an ultrasound estimated gestational at birth of more than 40 weeks. METHODS: Data were extracted from hospital-based records of all pregnant women who attended antenatal clinics on the Thai-Burmese border and who were more than 40 weeks pregnant. The effectiveness of castor oil to induce labour was expressed as time to birth and analysed with a Cox proportional hazards regression model. Measures associated with safety were fetal distress, meconium-stained amniotic fluid, tachysystole of the uterus, uterine rupture, abnormal maternal blood pressure during labour, Apgar scores, neonatal resuscitation, stillbirth, post-partum haemorrhage, severe diarrhoea and maternal death. Proportions were compared using Fisher's exact test. RESULTS: Of 612 women with a gestation of more than 40 weeks, 205 received castor oil for induction and 407 did not. The time to birth was not significantly different between the two groups (hazard ratio 0.99 (95% confidence interval: 0.81 to 1.20; n = 509)). Castor oil use was not associated with any harmful effects on the mother or fetus. CONCLUSIONS: Castor oil for induction of labour had no effect on time to birth nor were there any harmful effects observed in this large series. Our findings leave no justification for recommending castor oil for this purpose.

Thrombocytopaenia in pregnant women with malaria on the Thai-Burmese border.

BACKGROUND: Haematological changes associated with malaria in pregnancy are not well documented, and have focused predominantly on anaemia. Examined here is thrombocytopaenia in pregnant women infected with Plasmodium falciparum or Plasmodium vivax in a low transmission area on the north-western border of Thailand. METHODS: In this observational study we reviewed the platelet counts from routine complete blood count (CBC) in a cohort of healthy and malaria infected Karen pregnant women attending weekly antenatal clinics. A platelet count of 75,000/microL was the threshold at 2 standard deviations below the mean for healthy pregnant women used to indicate thrombocytopenia. Differences in platelet counts in non-pregnant and pregnant women were compared after matching for age, symptoms, malaria species and parasitaemia. RESULTS: In total 974 pregnant women had 1,558 CBC measurements between February 2004 and September 2006. The median platelet counts (/microL) were significantly lower in patients with an episode of falciparum 134,000 [11,000-690,000] (N = 694) or vivax malaria 184,000 [23,000-891,000] (N = 523) compared to healthy pregnant women 256,000 [64,000-781,000] (N = 255), P < 0.05 for both comparisons. Plasmodium falciparum and P. vivax caused a 34% (95% CI 24-47) and 22% (95% CI 8-36) reduction in platelet count, respectively. Pregnant compared to non pregnant women were at higher risk OR = 2.27 (95%CI 1.16-4.4) P = 0.017, for thrombocytopaenia. Platelets counts were higher in first compared with subsequent malaria infections within the same pregnancy. Malaria associated thrombocytopaenia had a median [range] time for recovery of 7 234567891011121314 days which did not differ by antimalarial treatment (P = 0.86), or species (P = 0.63) and was not associated with active bleeding. CONCLUSION: Pregnant women become more thrombocytopenic than non-pregnant women with acute uncomplicated malaria. Uncomplicated malaria associated thrombocytopaenia is seldom severe. Prompt antimalarial treatment resulted in normalization of platelet counts within a week.

A randomised controlled trial of artemether-lumefantrine versus artesunate for uncomplicated plasmodium falciparum treatment in pregnancy.

BACKGROUND: To date no comparative trials have been done, to our knowledge, of fixed-dose artemisinin combination therapies (ACTs) for the treatment of Plasmodium falciparum malaria in pregnancy. Evidence on the safety and efficacy of ACTs in pregnancy is needed as these drugs are being used increasingly throughout the malaria-affected world. The objective of this study was to compare the efficacy, tolerability, and safety of artemether-lumefantrine, the most widely used fixed ACT, with 7 d artesunate monotherapy in the second and third trimesters of pregnancy. METHODS AND FINDINGS: An open-label randomised controlled trial comparing directly observed treatment with artemether-lumefantrine 3 d (AL) or artesunate monotherapy 7 d (AS7) was conducted in Karen women in the border area of northwestern Thailand who had uncomplicated P. falciparum malaria in the second and third trimesters of pregnancy. The primary endpoint was efficacy defined as the P. falciparum PCR-adjusted cure rates assessed at delivery or by day 42 if this occurred later than delivery, as estimated by Kaplan-Meier survival analysis. Infants were assessed at birth and followed until 1 y of life. Blood sampling was performed to characterise the pharmacokinetics of lumefantrine in pregnancy. Both regimens were very well tolerated. The cure rates (95% confidence interval) for the intention to treat (ITT) population were: AS7 89.2% (82.3%-96.1%) and AL 82.0% (74.8%-89.3%), p = 0.054 (ITT); and AS7 89.7% (82.6%-96.8%) and AL 81.2% (73.6%-88.8%), p = 0.031 (per-protocol population). One-third of the PCR-confirmed recrudescent cases occurred after 42 d of follow-up. Birth outcomes and infant (up to age 1 y) outcomes did not differ significantly between the two groups. The pharmacokinetic study indicated that low concentrations of artemether and lumefantrine were the main contributors to the poor efficacy of AL. CONCLUSION: The current standard six-dose artemether-lumefantrine regimen was well tolerated and safe in pregnant Karen women with uncomplicated falciparum malaria, but efficacy was inferior to 7 d artesunate monotherapy and was unsatisfactory for general deployment in this geographic area. Reduced efficacy probably results from low drug concentrations in later pregnancy. A longer or more frequent AL dose regimen may be needed to treat pregnant women effectively and should now be evaluated. Parasitological endpoints in clinical trials of any antimalarial drug treatment in pregnancy should be extended to delivery or day 42 if it comes later. TRIAL REGISTRATION: Current Controlled Trials ISRCTN86353884.