Sputum smear microscopy referral rates and turnaround time in the Tonga Islands

Abstract

Setting: The National Tuberculosis Programme and the National Reference Laboratory, located on the main island of Tonga, Tongatapu, and three district hospital laboratories located on the outer islands.

Objectives: To compare Tongatapu with Tonga's outer islands with respect to sputum referral rates, numbers of samples per patient, sample quality, test results and time from sending sample to obtaining results and from obtaining results to treatment initiation.

Design: Retrospective study involving record review of laboratory and TB treatment registers in Tonga's four hospitals from 2003 to 2012.

Results: Of 3078 sputum samples submitted, 71.7% were of good quality. Sputum referral rates on Tongatupu were nearly twice as high as those on the outer islands (353 vs. 180 per 100 000 population). The mean smear turnaround times on Tongatapu and the outer islands were respectively 4.02 and 4.11 days. Of 83 positive cases, 91.2% were treated within a day in Tongatapu compared with 80% in the outer islands.

Conclusions: Referral rates for sputum smear testing differed in the main and the outer islands in Tonga, but turnaround times did not. Records of sputum quality and dates had limitations, necessitating interventions with TB-specific laboratory guidelines and registers. Further research is required to understand the differences in referral rates.

Efficient and timely detection of tuberculosis (TB) cases using quality-assured bacteriology is one of the pillars of the DOTS strategy recommended by the Stop TB Initiative.¹ Tonga, an island nation in the South Pacific that adopted the DOTS strategy in 1999, relies on sputum microscopy to diagnose TB, as culture and drug susceptibility testing (DST) are not locally available.² Tonga's sputum smear-positive TB notification rate was 15 per 100 000 population in 2000,³ and 6/100 000 in 2011.⁴ Although the number of cases may be declining, making elimination an attractive target, the effect of human immunodeficiency virus (HIV) infection, diabetes mellitus and tobacco on TB should also be considered, as they may hinder progress if they are not addressed adequately.^5–7 While HIV prevalence is low in Tonga, at 0.002%,⁸ 27.6% of the general population smoke tobacco daily and 16.4% have raised blood glucose levels.⁹ These factors can have a negative impact on TB control in Tonga; it is therefore crucial to ensure ongoing early case detection.¹⁰

All sputum smear microscopy in Tonga is performed by the National Reference Laboratory (NRL) of the Ministry of Health, which is located on Tonga's main island, Tongatapu. Three smaller district hospitals located on the outer island groups of Vava'u, Ha'apai and ‘Eua offer limited laboratory services and have to send sputum samples by boat or plane to the NRL. There has been no formal evaluation of turnaround times from diagnosis to treatment initiation or whether these differ for samples from Tongatapu and those from the outer islands.

The present study aimed to compare Tongatapu with the three outer island groups with respect to the numbers of samples sent for testing, sample quality, test results and times from sending the sample to a result being obtained and from obtaining a test result to treatment initiation.

METHODS

Study design

This was a retrospective study involving a review of laboratory records and TB treatment registers in all four hospitals in Tonga.

Setting

General

Tonga is an archipelago in the South Pacific Ocean that comprises 170 islands, 36 of which are inhabited. Tonga is administratively subdivided into five divisions: Tongatapu, ‘Eua, Ha’apai, Vava'u and the Niuas.¹¹ It is spread over 360 000 km² of ocean and has a total land area of 650 km².¹² The total population of Tonga is 103 036, of which 75 158 (72.9%) reside on Tongatapu, 14 936 (14.5%) on Vava'u, 6650 (6.5%) on Ha'apai, 5011 (4.9%) on ‘Eua and 1281 (1.2%) on the Niuas.¹³ The average population density is 157 persons/km², but can range from 280/km² in Tongatapu to only 23/km² in Niua.¹²

From Tongatapu, it is 303 km to Vava'u, 171 km to Ha'apai and 40 km to ‘Eua.¹⁴ There are 1–2 flights to the islands every day, with the exception of the Niuas, which has weekly flights. The flight time to Vava'u from Tongatapu is about 50 min, 30 min to Ha'apai and 8 min to ‘Eua.¹⁵ There is a daily ferry service to ‘Eua and a weekly service to Vava'u and Ha'apai.

Sputum smear microscopy

Tonga's National Tuberculosis Control Programme (NTP) guidelines recommend the collection of three sputum specimens (spot, morning, spot) for TB diagnosis. Sputum samples are collected at a TB clinic, a hospital, a community health centre or at the patient's home by trained health care workers such as TB coordinators and nurses, or the patients themselves. Sputum samples are labelled by health care workers at the time of collection and a completed microbiology request form accompanies each patient's sputum sample. In the outer islands, laboratory technicians are responsible for storing and packing sputum samples and transporting them by road to a plane or boat for transfer to the NRL. At Tongatapu, laboratory technicians or public health assistants are responsible for picking up the sputum samples and delivering them to the NRL. The sputum smear results are communicated back to the responsible physician or laboratory by telephone or fax; the NTP manager at the Communicable Disease Unit of the Ministry of Health is notified in case of positive acid-fast bacilli (AFB) results. Only a single positive result is required to confirm a diagnosis of TB and initiate treatment.²

Tonga's NTP undertakes internal monitoring of all laboratory activities. It also participates in external quality assurance (EQA) activities as part of the Pacific TB Laboratory Initiative (PATLAB), which includes on-site evaluation, panel testing and blinded slide rechecking.¹⁶ TB culture and DST are available off shore (LabPlus, Auckland, New Zealand) if necessary. Although the NRL has a dedicated register for TB, the outer island laboratories do not. Information about the collection, transportation and results of sputum samples is recorded in a register that also includes information on other samples such as urine and blood.

Participants

The study included all cases with presumed TB in Tonga recorded in the laboratory registers over a 10-year period from 1 January 2003 to 31 December 2012.

Variables, data collection and validation

Data were collected from the general laboratory and TB registers held at the three district hospitals in Tonga's outer island groups and from the TB laboratory and treatment register at the NRL. Variables included age, sex, number and quality of sputum samples collected, sputum smear status, geographic location of sample collection, dates when samples were sent to the NRL, dates when results were reported and, for smear-positive cases, the date of treatment initiation. Positive smear results were graded as scanty, 1+, 2+ or 3+.

Turnaround time was defined as the length of time from the date on which the sample was sent to the NRL until the date of obtaining the result. The time to treatment initiation was defined as the length of time from the date of obtaining the result to the date of treatment initiation. Sputum quality was defined as good (specimen mucoid, purulent or blood stained) or poor (specimen thin, watery or composed largely of bubbles or saliva).

Selected variables for smear-positive cases were validated by cross-checking laboratory records and patient treatment cards.

Referral rates were calculated by the total number of samples divided by the total population of the main island vs. the outer island groups together. Denominator populations were estimated by back and forward extrapolation from the 2006 and 2011 national census, assuming a growth rate of 0.4% per annum.¹³ According to the census, age structures and male to female ratio on the main island have consistently been similar to those on the outer islands.

Analysis and statistics

Data were collected and double-entered by independent encoders from the registries into an electronic structured questionnaire using EpiData Version 3.1 (EpiData Association, Odense, Denmark) and compared for discordance. The time from when the sputum sample was sent to obtaining the result (or treatment initiation for patients with sputum-positive TB) was represented in days. An acceptable turnaround time of 1 day was adopted from the World Health Organization (WHO) recommendations.¹⁷ Study outcomes based on variations from the acceptable turnaround time were then compared between Tongatapu and the outlying islands using the χ² test.

Ethics

Ethics approval was obtained from the Ethics Advisory Group of the International Union Against Tuberculosis and Lung Disease, Paris, France, and the Ministry of Health Ethics Committee in Tongatapu, Tonga.

RESULTS

The location of the laboratory sending the sample was not recorded for 13 patients, who were therefore excluded from the analysis, leaving a patient population of 1354. Table 1 shows the basic characteristics and number of sputum samples submitted by patients suspected of pulmonary TB in Tongatapu and the outer islands. Sex was recorded for 1343 patients, of whom 547 (40.4%) were female. In the outer islands, 46.9% were female compared with 39.6% in Tongatapu (P = 0.049). Age was recorded for 1278 patients only. The median age was 60 years (range 1–100, mean 53.8 years, standard deviation [SD] 22.6); 78 (5.8%) were in the 0–14 years age group, 231 (17.1%) 15–34 years, 412 (30.4%) 35–64 years and 557 (41.1%) ≥ 65 years. There was no significant difference in the age distribution of cases of presumed TB between the main and outer islands (P = 0.945).

TABLE 1.

Number of sputum samples submitted and results among patients with presumed TB, Tonga, 2003–2012

Number of sputum smears

A total of 3078 sputum samples were sent for testing; 986 patients provided a second sputum sample and 738 a third. On Tongatapu, 71.8% provided a second sputum sample and 54% a third. In the outer islands, 78.5% provided a second sputum sample and 57% a third.

Referral rates

The sputum referral rate for Tongatapu was 353/100 000 compared to 180/100 000 for the outer islands (the Figure).

FIGURE.

Sputum referral rates for Tongatapu and the outer islands, Tonga, 2003–2012.

Sputum smear quality

Table 2 shows sputum quality and time from sending sputum sample to treatment initiation in Tongatapu and the outer islands. Of 3078 smears, 2208 (71.7%) were recorded as being of good quality and 175 (5.7%) of poor quality. For 695 (22.6%) samples, the quality was not recorded. There were no significant differences between the main and outer islands with respect to quality (P = 0.85), and between the first, second and third smears (P = 0.67). However, on the whole, smears from children (aged 0–14 years) were less likely to be of good quality than those from older age groups (63.6% vs. 72.5%, P = 0.0021).

TABLE 2.

Sputum quality and date from sending sputum to treatment initiation in Tongatapu and the outer islands of Tonga, 2003–2012

Time between sending sputum samples and obtaining results

Of all the sputum samples sent for testing, 80 (2.7%) had information missing on dates, and were therefore excluded from turnaround time analysis, leaving 2998 smears. For smears from Tongatapu, the mean turnaround time was 4.02 vs. 4.11 days for smears sent from the outer islands (SD 3.74, range 0–27 vs. SD 3.47, range 0–17, P = 0.62). The median turnaround time for the study population was 3 days, with 8.8% (n = 263) of smears reported within 1 day and 74.5% reported within 5 days.

Time between obtaining test results and treatment initiation

Of the 83 sputum smear-positive patients, 68 were from Tongatapu and 15 from the outer islands (6.0% vs. 7.0% of presumptive TB cases, P = 0.34). Overall, 89.2% started on treatment within 1 day: 91.2% in Tongatapu vs. 80% in the outer islands (P = 0.21).

DISCUSSION

This is the first study in Tonga to evaluate and compare referral rates, turnaround times for sputum smear microscopy and treatment initiation, and sputum quality in the main and outer islands of Tonga. Referral rates for sputum smear testing from the outer islands were much lower than those from the main island, where the referral laboratory is located; individuals with presumptive TB from the outer islands were more likely to be women. While sputum quality was worse overall for children, there were no significant differences between the main and the outer islands with respect to sputum quality or turnaround times. Smear-positive patients were less likely to be started on treatment within 1 day if they were from the outer islands, but the difference was not statistically significant.

We are not aware of any other studies to have examined referral rates for sputum smear microscopy by geographic location. This was not explained by any difference in the number of sputum samples per patient, and the proportion of smear-positive suspects was not significantly different. The fact that there was no difference in the proportion of positive smears strongly suggests that the incidence of TB notifications in the outer islands is much lower than on Tongatapu. Lower incidence in remote locations has been reported elsewhere, in both developing¹⁸ and industrialised countries.¹⁹ It is not certain whether or not the differences in incidence rates obtained using passive case detection are real: active case detection is necessary to resolve the issue.²⁰ It is highly likely that reduced access to diagnostic services in the outlying islands leads to underdiagnosis and low referral rates for sputum smears.²¹

In settings using passive case detection, more TB cases are male than female; the male to female ratio is more evenly balanced when active case detection is used.²² It should be noted that around 60% of study samples from Tongatapu were from males, whereas just over 50% of sputum samples were from males in the outer islands. This may be a chance finding, but requires further research. While the differences in turnaround times were not statistically significant, the fact that 20% of newly diagnosed TB cases in the outer islands are not placed on anti-tuberculosis treatment within a day suggests that there is room for improvement in treatment initiation.

This study has exposed some issues with the recording and reporting practices used for sputum smear microscopy in Tonga. In nearly 22.6% of the samples submitted, sputum quality was not recorded in the laboratory register. Where quality was recorded, 5.7% of samples were recorded as being poor, although this was not more common among samples from the outer islands. Incomplete data entry also affects the accuracy and comprehensiveness of TB laboratory and treatment registers.^23,24 Furthermore, key data related to the process of sputum smear microscopy—for example, key dates in the process of collection, transportation and reception of samples and reporting results—had not been consistently and rigorously recorded over the 10-year period. Without this information, the NTP cannot monitor turnaround times in the diagnostic and treatment initiation process or determine when delays or other problems occur. Laboratories on the outer islands tend to wait for a full set of samples from each patient before sending them to the NRL. This practice of ‘batching’ could not be clearly documented in this study, as the date of sample collection was not recorded in the laboratory registers of the outer islands. It is possible that significant delays occur between the collection of the first and the third sample. Efficient TB diagnosis is dependent on sputum being properly collected and transported and on the correct communication of results.²⁵

The strengths of the study are that all four laboratories in Tonga were included, making it a large, nationally representative sample for a 10-year period. In addition, the protocol and reporting follow STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines.²⁶ Limitations are related to the operational nature of the research conducted, mainly missing data. In particular, the turnaround time from the date of sputum collection could not be calculated. Further research is required to determine if active case finding should be performed in the Tongan outer islands. Steps could be taken to ensure completeness of data recorded on age, sex, name of submitting laboratory and dates. Training should be considered to enhance sputum quality along with enhanced routine supervision of all laboratories. The NTP should also consider creating TB-specific laboratory guidelines, creating laboratory registers dedicated to TB and updating the NTP treatment guidelines to include indications on an acceptable sputum turnaround time.