Human Papilloma Virus key papers: testing strategy, impact of immunisation, women’s knowledge (PNG)

HPV and cervical cancer remain incredibly important topics for detailed study by all post graduates.  Again, these papers are available as free text via the PUBMED links provided.

  • Field Evaluation of Xpert HPV Point-of-Care Test for Detection of Human Papillomavirus Infection by Use of Self-Collected Vaginal and Clinician-Collected Cervical Specimens. J Clin Microbiol. 2016 Jul;54(7):1734-7.  Toliman P et al.

An important paper to review: “Self-collected vaginal specimens had excellent agreement with clinician-collected cervical specimens for the detection of hrHPV infection using the Xpert HPV test. ”   

[In other unpublished research from PNGIMR and Burnet Institute, abnormal acetic acid colposcopy-directed POC Xpert HPV testing was effective at enabling a same day cryotherapy approach to deal with HPV positive cervicopathology. 

  • Human papillomavirus vaccination: the population impact. Lee LY, Garland SM. F1000Res. 2017 Jun 12;6:866.An essential read – free full text and reasonably short. Provides an overview of all the HPV immunisation and its impact as a prophylactic measure, contrasting available data from around the world.

“This mini-review focuses on the need for HPV vaccine implementation in Asia given the substantial disease burden and underuse of HPV vaccines in LMICs in this region. In addition, the progress towards HPV vaccine introduction, and barriers preventing further rollout of these essential, life-saving vaccines are also discussed in this article.”

  • Ambiguous bodies, uncertain diseases: knowledge of cervical cancer in Papua New Guinea. Ethn Health. 2017 Feb 3:1-23. Kelly-Hanku A et al.
Very important qualitative research. “..found that knowledge and awareness about cervical cancer were poor …  clear need to improve understanding of the female reproductive organs in order that people, women in particular, can be better informed about cervical cancer and ultimately better receptive to intervention strategies.”

The two yearly Pap test for women aged 18 to 69 will change to a five yearly human papillomavirus (HPV) test for women aged 25 to 74. Women will be due for the first Cervical Screening Test two years after their last Pap test. The changes include:

  • women will be invited when they are due to participate via the National Cancer Screening Register
  • the Pap smear will be replaced with the more accurate Cervical Screening Test
  • the time between tests will change from two to five years
  • the age at which screening starts will increase from 18 years to 25 years
  • women aged 70 to 74 years will be invited to have an exit test.

Genome organization of human papillomavirus type 16, one of the subtypes known to cause cervical cancer (E1-E7 early genes, L1-L2 late genes: capsid)

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STDs in the Pacific and elsewhere: some essential research papers to review

Most of these have free text available via the PUBMED link and come from projects lead by PNGIMR and the Kirby and Burnet Institutes.  Remember as well to use the WHO STD Laboratory Manual as your microbiological study reference for these diseases and their diagnosis.  If you have trouble getting the full papers, please contact me.

  • A novel point-of-care testing strategy for sexually transmitted infections among pregnant women in high-burden settings: results of a feasibility study in Papua New Guinea. BMC Infect Dis. 2016 Jun 6;16:250. doi: 10.1186/s12879-016-1573-4.

The utility of the GenXpert platform for diagnosis of a range of STDs is apparent. 

  • Prevalence and risk factors of Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis and other sexually transmissible infections among women attending antenatal clinics in three provinces in Papua New Guinea: a cross-sectional survey . Sex Health. 2016 Oct;13(5):420-427. doi: 10.1071/SH15227.
  • Prevalence and risk factors for Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis infection in pregnant women in Papua New Guinea. Sex Transm Infect. 2015 May;91(3):194-200. doi: 10.1136/sextrans-2014-051670. Epub 2014 Oct 13.
  • Surveillance of antibiotic resistance in Neisseria gonorrhoeae in the WHO Western Pacific and South East Asian Regions, 2009. Commun Dis Intell Q Rep. 2011 Mar;35(1):2-7.

An important issue for laboratories in the Pacific – we need to ensure that culture methods are in place and that regular surveys of antimicrobial susceptibility take place- this enables appropriate guidelines to be put in place for drug supply and treatment. 

The utility of routine testing of self-collected anorectal samples, even in clients who do not admit to anal intercourse. 

  • Dorsal longitudinal foreskin cut is associated with reduced risk of HIV, syphilis and genital herpes in men: a cross-sectional study in Papua New Guinea. J Int AIDS Soc. 2017 Apr 3;20(1):21358.

“In this large cross-sectional study, men with a dorsal longitudinal foreskin cut were significantly less likely to have HIV, HSV-2 and syphilis compared with uncut men, despite still having a complete (albeit morphologically altered) foreskin. …Exposure of the penile glans and inner foreskin appear to be key mechanisms by which male circumcision confers protection.”

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Leishmaniasis case report and overview

From Stark et al, case report Medical Journal of Australia 2007 : 

A: Non-healing New World cutaneous leishmaniasis ulcer on the left forearm.

B: Metacyclic Leishmania promastigotes in culture medium, Day 7.The parasites have a characteristic coiled, highly motile flagellum at the apical end of an elongated body (10–20 mm in length) containing a round nucleus and rod-shaped kinetoplast.

C: Molecular banding pattern in agarose gel after PCR analysis. The banding pattern resulting from restriction fragment length polymorphism PCR analysis was consistent with Leishmania braziliensis DNA (M: a commercial 100-base-pair molecular marker [EZ Load 100 bp molecular ruler; Bio-Rad Laboratories, Hercules, Calif, USA]; 1: L. braziliensis control strain; 2: patient sample).

D: Healed ulcer, 4 weeks after treatment with amphotericin B.

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Toxoplasma, Entamoeba histolytica, Amoebic meningoencephalitis & keratitis

Toxoplasmosis 

Relevant manifestations to consider further:

  • congenital – diagnosis – excellent recent guide 
  • reactivation in an immunocompromised (deficient cell-mediated immunity ) patient  such as someone with advanced HIV – then cerebral abscess (may be multiple), retinitis or pneumonitis (similar picture to pneumocystis) occur – direct tissue demonstration of tachyzoites required generally (PCR also possible).   Presumptive diagnosis usually made in HIV patient with cerebral abscess, usually after checking to confirm IgG seropositivity – therapeutic trial of antibiotic therapy then occurs – if no response then other differentials become more relevant – e.g. cerebral lymphoma.

Seroprevalence of anti-Toxoplasma gondii antibodies in HIV/AIDS patients and healthy blood donors at the Port Moresby General Hospital, Papua New Guinea.P N G Med J. 2012 Mar-Dec;55(1-4):88-93.   301 patients (181 HIV positive); overall antibody prevalence rate of 53% in the population and a significantly higher infection rate amongst HIV-positive patients.

Entamoeba histolytica

Note that if someone is a carrier (passes cysts of Entamoeba), then if they develop diarrhoea from some other cause, the cysts will form trophozoites – this does NOT mean the patient has amoebic dysentery!

Amoebic meningoencephalitis and keratitis

Primary amoebic meningoencephalitis in North Queensland: the paediatric experience. Med J Aust. 2016 Oct 3;205(7):325-8. Primary amoebic meningoencephalitis (PAM) is a fulminant, diffuse haemorrhagic meningoencephalitis caused by Naegleria fowleri, with an almost invariably fatal outcome. In Australia and the developed world, PAM remains a rare disease, although it is very likely that large numbers of cases go undetected in developing countries. N. fowleri is a thermophilic, free-living amoeba with a worldwide distribution. It is acquired when contaminated fresh water is flushed into the nose and penetrates the central nervous system via the cribriform plate. Clinical features are similar to those of bacterial meningitis, but it does not respond to standard therapy and rapid progression to death occurs in most cases. Some survivors have been reported; these patients received early treatment with amphotericin B in combination with a variety of other medications. Our review describes the local and worldwide experience of this disease and its clinical features, and discusses the associated diagnostic challenges. We hope that by detailing the local response to a recent case, and the outcomes of our public health campaign, we can improve the knowledge of this rare disease for doctors working in rural and remote Australia.

Primary amoebic meningoencephalitis in the Western Province. P N G Med J. 1991 Jun;34(2):87-9.  Six cases of primary amoebic meningoencephalitis were diagnosed and treated at the Balimo Health Centre between December 1986 and September 1988. This disease has not previously been reported in Papua New Guinea although from information derived from other studies it should be occurring in the lowlands of Papua New Guinea from time to time. Although less than optimum treatment was given to the early cases the case fatality rate in the series was only 66%. This compares very favorably with a case fatality rate of nearly 100% from other studies. Early diagnosis and prompt treatment should help to reduce mortality.

Strategies for the prevention of contact lens-related Acanthamoeba keratitis.  Ophthalmic Physiol Opt. 2016 Mar;36(2):77-92.  Acanthamoeba keratitis is a severe, often sight threatening, corneal infection which in Western countries is predominantly seen in daily wear of contact lenses. This review aims to summarise the pathobiology and epidemiology of contact lens-related Acanthamoeba keratitis, and to present strategies for prevention, particularly with respect to modifiable risk factors in contact lens wear.

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Coccidian enteric parasites- Cryptosporidium and Cyclospora

FERGUSON 2011 Coccidian enteric parasites  (includes references relevant to Nepal)

  • Rapid diagnostic tests for Cryptosporidium are effective- often combined with a giardia test.   However as the illness is self-limited in the immunocompetent, testing probably not relevant. Highly relevant for immunocompromised patients where treatment is required.
  •  Life cycle of Cryptosporidium.
  • Two PNG- associated references:

Seroepidemiology of cryptosporidiosis in children in Papua New Guinea and Australia.Groves VJ1, Lehmann D, Gilbert GLEpidemiol Infect. 1994 Dec;113(3):491-9.

Enzyme immunoassays (EIA) were used to measure serum antibodies to Cryptosporidium in four immunocompetent adults with recent proven cryptosporidial infection, 379 healthy children and 73 adult volunteers in Melbourne, Australia, and 205 children in Papua New Guinea (PNG) (47 healthy children; 158 with pneumonia). Antibodies peaked 3-6 weeks after infection and fell to baseline within a few months. A high level (5000 EIA units/ml) or a significant change between paired sera, of IgG or IgM, were taken as evidence of recent infection and found in 24% of PNG children and in 8% of children and 5% of adults in Melbourne. Among PNG children with pneumonia who had high cryptosporidial antibody levels, those with measles (6/8) were significantly more likely (P = 0.002) to have diarrhoea than the remainder (4/28). Symptomatic cryptosporidiosis may be associated with transient immune suppression due to viral infection. This study indicates that serological surveys can contribute to an understanding of the epidemiology of cryptosporidosis.

Cryptosporidium species in sheep and goats from Papua New Guinea. Exp Parasitol. 2014 Jun;141:134-7. 

Species of Cryptosporidium are extensively recognised as pathogens of domesticated livestock and poultry, companion animals, wildlife, and are a threat to public health. Little is known of the prevalence of Cryptosporidium spp. in humans, domesticated animals or wildlife in Papua New Guinea (PNG). The aim of the present study was to screen sheep and goats for Cryptosporidium using molecular tools. A total of 504 faecal samples were collected from sheep (n=276) and goats (n=228) in village, government and institutional farms in PNG. Samples were screened by nested PCR and genotyped at the 18S rRNA and at the 60kDa glycoprotein (gp60) loci. The overall prevalences were 2.2% for sheep (6/278) and 4.4% (10/228) for goats. The species/genotypes identified were Cryptosporidium hominis (subtype IdA15G1) in goats (n=6), Cryptosporidium parvum (subtypes IIaA15G2R1and IIaA19G4R1) in sheep (n=4) and in goats (n=2), Cryptosporidium andersoni (n=1) and Cryptosporidium scrofarum (n=1) in sheep, Cryptosporidium xiao (n=1) and Cryptosporidium rat genotype II (n=1) in goats. This is the first report of Cryptosporidium spp. identified in sheep and goats in PNG. Identification of Cryptosporidium in livestock warrants better care of farm animals to avoid contamination and illness in vulnerable population. The detection of zoonotic Cryptosporidium in livestock suggests these animals may serve as reservoirs for human infection.

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Plasmodium species (malaria)

Recent CPHL malaria workshop materials – make sure you have a copy and review same.

Short answer questions to guide your further reading: 

  1. What rapid diagnostic tests are in use and what is their performance?  Check the kit inserts and share what you find please.  Also visit WHO Malaria RDT resource page.
  2. What are the PNG-specific current malaria treatment guidelines? (not necessarily what is in the old STG)
  3. What are the expected changes to be found on fbc and film examination of a patient with malaria?
  4. Describe artemisinin resistance – incidence and impact – see this WHO page.
  5. Describe current progress towards malaria vaccines – yes! there is a candidate vaccine that works to prevent malaria in children – pilot implementation project in three countries at present.

Scan Pubmed to browse recent research on malaria published by PNG projects.  Select a paper for your next journal club!

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Infection control guidelines – Pacific Nations

PPHSN Infection Prevention and  Control Guidelines –  2010 

These are likely to be updated before too long.  They are produced by PICNet – Pacific regional Infection Control Network.

Updated PNG Infection Control Guidelines are expected soon.

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Hepatitis E- more important issues for Pacific nations

Please see this previously posted presentation from Prof. Josh Davis about HEV– an excellent overview – tells the Australian part of the story – endemicity in pigs (genotype 3) and local foodborne outbreaks.

The only survey of seroprevalence in the Pacific was published in 2014, referencing data acquired from Kiribati, PNG and Fiji 2003-5 – essential reading.  Overall 15% seroprevalence in PNG, higher in the highlands.  It references some data showing that genotype 3 has been found in pigs in New Caledonia.

Rapid testing reference referred today by Joe is here – an Italian study – almost all cases were genotype 1 which may make the tests less reliable in PNG.  Another good paper for your journal club.

As discussed, there will be an unknown morbidity occurring in PNG, especially in pregnant women and it is almost certain that a large zoonotic reservoir exists. Ripe for some proper research and important that local testing is established. 

According to WHO, a recombinant effective vaccine to prevent hepatitis E virus infection has been developed and is licensed in China, but is not yet available elsewhere.

PNG should coloured red! 

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“UTI” – Requiem for a Heavyweight – a landmark paper

A really important paper to consider closely – i will send on a PDF via email as general access not available.  This editorial from the BMJ is a worthwhile read as well.

AIMED - Let's talk about antibiotics

A recent paper, “Urinary Tract Infection”-Requiem for a Heavyweight  by Dr Thomas Finucaine skillfully unpacks many key issues, coupling this with a consideration of the emerging knowledge of the urinary microbiome and virome, suggesting that the term “UTI” might better be referred to as a “urinary dysbiosis”.  The paper is worth a detailed read – here is the start of the abstract –

“Urinary tract infection” (“UTI”) is an ambiguous, expansive, overused diagnosis that can lead to marked, harmful antibiotic overtreatment. “Significant bacteriuria,” central to most definitions of “UTI,” has little significance in identifying individuals who will benefit from treatment. “Urinary symptoms” are similarly uninformative. Neither criterion is well defined. Bacteriuria and symptoms remit and recur spontaneously. Treatment is standard for acute uncomplicated cystitis and common for asymptomatic bacteriuria, but definite benefits are few. Treatment for “UTI” in older adults with delirium and bacteriuria is widespread but no evidence supports…

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You are what you eat – or should our gut microbiome be considered an important body system in its own right?

AIMED - Let's talk about antibiotics

Guest posting: Assoc. Prof. Josh Davis,  Principal Research Fellow/NHMRC Career Development Fellow, Menzies School of Health Research, Senior Staff Specialist Infectious Diseases Physician, John Hunter Hospital, Conjoint Professor School of Medicine and Public Health, University of Newcastle

The diverse bacterial communities which live in our gastrointestinal tract (primary in the colon), are collectively known as the “gut microbiota” and their collective genes are termed the “microbiome“.  A majority of the bacterial species cannot cultivated and require direct molecular techniques to ennumerate them.  Consideration of the microbiome is extremely topical in many fields of health-related research. At the recent major annual meeting of the American Society for Microbiology (ASM Microbe), the gut microbiome had its own stream (no pun intended – and the colour coding wasn’t brown) within the conference program, containing scores of research presentations in this field. In fact, one conference delegate, science writer and microbiologist Ed Yong, insisted…

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